Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanis...Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Ischemic stroke is one of the major causes of long-term disability and mortality worldwide.It results from an interruption in the cerebral blood flow,triggering a cascade of detrimental events like oxidative stress,mi...Ischemic stroke is one of the major causes of long-term disability and mortality worldwide.It results from an interruption in the cerebral blood flow,triggering a cascade of detrimental events like oxidative stress,mitochondrial dysfunction,neuroinflammation,excitotoxicity,and apoptosis,causing neuronal injury and cellular death.Melatonin,a pleiotropic indoleamine produced by the pineal gland,has multifaceted neuroprotective effects on stroke pathophysiology.Interestingly,the serum melatonin levels are associated with peroxidation and antioxidant status,along with mortality score in patients with severe middle cerebral artery infarction.Melatonin exhibits strong antioxidant,anti-inflammatory,and anti-apoptotic properties and preserves mitochondrial function and homeostasis.Several preclinical studies have shown that melatonin administration conserves blood-brain barrier integrity,reduces infarct size,and edema.These mechanisms contribute to minimizing tissue damage and improving the neurological outcomes following ischemic events.Therefore,the present review evaluates evidence from experimental studies furthered with limited clinical investigations and explores the mechanistic pathways ofmelatonin functions to establish its therapeutic potential in stroke management.展开更多
Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroa...Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.展开更多
Acute ischemic stroke remains a significant health concern owing to the limited efficacy of current therapeutic options.In recent years,Neuregulin-1 has exhibited promising neuroprotective effects in cerebral ischemia...Acute ischemic stroke remains a significant health concern owing to the limited efficacy of current therapeutic options.In recent years,Neuregulin-1 has exhibited promising neuroprotective effects in cerebral ischemia.However,the sources and functions of Neuregulin-1 have not yet been fully understood,which hinders its translation and broad application.Here,we collected paired clot and peripheral blood samples from patients with acute ischemic stroke to determine the sources of Neuregulin-1.In addition,we established an in vivo transient middle cerebral artery occlusion mouse model to investigate the therapeutic effects of Neuregulin-1 and its underlying molecular biological mechanisms.We observed a significant elevation in serum Neuregulin-1 levels among patients with acute ischemic stroke that correlated with severity of neurological impairment and clinical outcome.Using single-cell sequencing,we identified Neuregulin-1-positive macrophages among peripheral blood mononuclear cells that produced Neuregulin-1 post-ischemia.In addition,Neuregulin-1 promoted repair of the infarcted area,alleviating neuronal and myelin damage and improving overall behavioral recovery in mice.We found that Neuregulin-1 may exert these neuroprotective effects by promoting angiogenesis in the infarct area,and that this effect is mediated by Akt/mTOR/VEGF-dependent signaling.Our findings suggest that peripheral macrophages are a source of Neuregulin-1 post-stroke.Neuregulin-1 exerts its neuroprotective effects by promoting angiogenesis via Akt/mTOR/VEGF-dependent signaling,showing promising clinical translation potential.展开更多
Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In t...Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.展开更多
Recent studies have indicated that stroke can lead to neuronal iron overload and lipid peroxidation.Lycium barbarum glycopeptide,which has a low molecular weight and potent antioxidant properties,may mitigate ferropto...Recent studies have indicated that stroke can lead to neuronal iron overload and lipid peroxidation.Lycium barbarum glycopeptide,which has a low molecular weight and potent antioxidant properties,may mitigate ferroptosis in stroke.We hypothesized that Lycium barbarum glycopeptide can effectively mitigate iron overload within ischemic neurons due to its robust antioxidant properties.The aims of this study were to investigate the effects of Lycium barbarum glycopeptide on ferroptotic damage following brain ischemia and explore the underlying mechanisms.A rat model of middle cerebral artery occlusion was established using the intraluminal filament method,and the rats were treated with Lycium barbarum glycopeptide for 7 consecutive days,beginning 24 hours after ischemia.Liproxstatin-1,a ferroptosis inhibitor,and Erastin,a ferroptosis activator,were used as controls.We found that treatment with Lycium barbarum glycopeptide resulted in significant reductions in infarct volume(as detected by triphenyltetrazolium chloride staining staining and magnetic resonance imaging)and neuronal death(as measured by Nissl staining),as well as improvements in sensory and motor functions in rats subjected to middle cerebral artery occlusion.Furthermore,treatment with Lycium barbarum glycopeptide alleviated anxiety and depression-like behaviors and improved memory.Additionally,Lycium barbarum glycopeptide effectively reduced the iron ion content in the ischemic penumbra of the cortex.Moreover,treatment with Lycium barbarum glycopeptide downregulated the expression of ferroptotic and oxidant proteins such as transferrin receptor 1,divalent metal transporter 1,and Acyl-CoA synthetase long-chain family member 4 and upregulated the expression of anti-ferroptotic and antioxidant proteins such as ferroportin 1,solute carrier family 7 member 11,glutathione,and glutathione peroxidase 4.However,these beneficial effects were reversed when ferroptosis was induced with the activator Erastin.Therefore,the positive effects of Lycium barbarum glycopeptide in ischemic stroke are likely mediated through activation of the anti-ferroptotic pathway and the antioxidative System Xc-glutathione-glutathione peroxidase 4 pathway.Overall,our findings highlight the potential use of Lycium barbarum glycopeptide as a neuroprotective agent targeting both ferroptosis and oxidation to decrease ischemic brain damage.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fun...Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammat...Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Objective:To explore the interventional room nursing and its application effects in patients with ischemic stroke treated with tirofiban combined with direct thrombectomy.Methods:A total of 61 patients with ischemic s...Objective:To explore the interventional room nursing and its application effects in patients with ischemic stroke treated with tirofiban combined with direct thrombectomy.Methods:A total of 61 patients with ischemic stroke admitted to our hospital from June 2024 to June 2025 were selected and divided into two groups using the red and blue ball method:the control group(n=30,receiving routine interventional room nursing)and the observation group(n=31,receiving additional tirofiban medication-specific nursing+individualized interventional nursing on the basis of routine nursing).The cerebral hemodynamic indicators,adverse reactions,effectiveness of complication nursing,and nursing satisfaction were compared between the two groups.Results:After 7 days of treatment,the observation group had lower cerebrovascular peripheral resistance and higher mean blood flow velocity and mean blood flow volume compared to the control group(all p<0.05).The observation group had a higher effectiveness rate of complication nursing than the control group,with a statistically significant difference(p<0.05).The nursing satisfaction in the observation group(96.77%)was higher than that in the control group(80.00%),with a statistically significant difference(χ^(2)=4.223,p=0.040<0.05).Conclusion:Tirofiban combined with direct thrombectomy can significantly improve cerebral hemodynamics,enhance the effectiveness of complication nursing,and increase patient satisfaction in patients with ischemic stroke.展开更多
White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet li...White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and dep...BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.展开更多
Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the developmen...Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.展开更多
Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated ne...Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.展开更多
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the Natural Science Foundation of Heilongjiang Province,No.YQ2021H011(to QL)China Postdoctoral Science Foundation,Nos.2020M670925,2022T150172(to QL)+2 种基金Postdoctoral Foundation of Heilongjiang Province,Nos.LBH‐Z19027,LBH‐TZ2019(to QL)Institute Cultivation Fund,No.PYMS2023-1(to QL)Natural Science Foundation of Jiangsu Province,No.BK20241233(to YL).
文摘Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
基金supported by Chulabhorn Graduate Institute(Fundamental Fund by National Science Research and Innovation Fund(NSRF):fiscal year 2025)(FRB680079/0518 Project code 209041)Chulabhorn Graduate Institute(651-AB01).
文摘Ischemic stroke is one of the major causes of long-term disability and mortality worldwide.It results from an interruption in the cerebral blood flow,triggering a cascade of detrimental events like oxidative stress,mitochondrial dysfunction,neuroinflammation,excitotoxicity,and apoptosis,causing neuronal injury and cellular death.Melatonin,a pleiotropic indoleamine produced by the pineal gland,has multifaceted neuroprotective effects on stroke pathophysiology.Interestingly,the serum melatonin levels are associated with peroxidation and antioxidant status,along with mortality score in patients with severe middle cerebral artery infarction.Melatonin exhibits strong antioxidant,anti-inflammatory,and anti-apoptotic properties and preserves mitochondrial function and homeostasis.Several preclinical studies have shown that melatonin administration conserves blood-brain barrier integrity,reduces infarct size,and edema.These mechanisms contribute to minimizing tissue damage and improving the neurological outcomes following ischemic events.Therefore,the present review evaluates evidence from experimental studies furthered with limited clinical investigations and explores the mechanistic pathways ofmelatonin functions to establish its therapeutic potential in stroke management.
基金supported by the National Natural Science Foundation of China,Nos.82174496(to NW),82374574(to NW),82302865(to LL)Shanghai Science and Technology Committee Sailing Program,Nos.23YF1403800(to LL),23YF1405200(to YX)Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance,No.SHDC22023304(to YW).
文摘Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.
基金Chongqing Technology lnnovation and Application Development Program,No.CSTB2023TIAD-KPX0061(to ZZ)the National Natural Science Foundation of China,Nos.81971130(to ZZ),82201464(to XC).
文摘Acute ischemic stroke remains a significant health concern owing to the limited efficacy of current therapeutic options.In recent years,Neuregulin-1 has exhibited promising neuroprotective effects in cerebral ischemia.However,the sources and functions of Neuregulin-1 have not yet been fully understood,which hinders its translation and broad application.Here,we collected paired clot and peripheral blood samples from patients with acute ischemic stroke to determine the sources of Neuregulin-1.In addition,we established an in vivo transient middle cerebral artery occlusion mouse model to investigate the therapeutic effects of Neuregulin-1 and its underlying molecular biological mechanisms.We observed a significant elevation in serum Neuregulin-1 levels among patients with acute ischemic stroke that correlated with severity of neurological impairment and clinical outcome.Using single-cell sequencing,we identified Neuregulin-1-positive macrophages among peripheral blood mononuclear cells that produced Neuregulin-1 post-ischemia.In addition,Neuregulin-1 promoted repair of the infarcted area,alleviating neuronal and myelin damage and improving overall behavioral recovery in mice.We found that Neuregulin-1 may exert these neuroprotective effects by promoting angiogenesis in the infarct area,and that this effect is mediated by Akt/mTOR/VEGF-dependent signaling.Our findings suggest that peripheral macrophages are a source of Neuregulin-1 post-stroke.Neuregulin-1 exerts its neuroprotective effects by promoting angiogenesis via Akt/mTOR/VEGF-dependent signaling,showing promising clinical translation potential.
基金supported by Shanghai Shenkang Center Demonstration Research Ward Construction,No.SHDC2022CRW010(to MF)Shanghai Shenkang Center Medical Enterprise Integration and Innovation Collaborative Special Project,No.SHDC2022CRT018(to MF)+4 种基金Shanghai Health System Key Supported Discipline-Rehabilitation Medicine,No.2023ZDFC0301(to JT)Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine,No.23KFL009(to JT)Shanghai Postdoctoral Excellence Program,No.2022515(to CY)Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan,No.23YF1447600(to CY)China Postdoctoral Science Foundation,No.2023M732338(to CY).
文摘Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.
基金National Nature Science Foundation of China,No.30971530(to YR)The National 111 Project,No.B14036(to KFS)Key Basic Study and Functional Product Research of Wolfberry Grant of Ningxia Hui Autonomous Region(to KFS).
文摘Recent studies have indicated that stroke can lead to neuronal iron overload and lipid peroxidation.Lycium barbarum glycopeptide,which has a low molecular weight and potent antioxidant properties,may mitigate ferroptosis in stroke.We hypothesized that Lycium barbarum glycopeptide can effectively mitigate iron overload within ischemic neurons due to its robust antioxidant properties.The aims of this study were to investigate the effects of Lycium barbarum glycopeptide on ferroptotic damage following brain ischemia and explore the underlying mechanisms.A rat model of middle cerebral artery occlusion was established using the intraluminal filament method,and the rats were treated with Lycium barbarum glycopeptide for 7 consecutive days,beginning 24 hours after ischemia.Liproxstatin-1,a ferroptosis inhibitor,and Erastin,a ferroptosis activator,were used as controls.We found that treatment with Lycium barbarum glycopeptide resulted in significant reductions in infarct volume(as detected by triphenyltetrazolium chloride staining staining and magnetic resonance imaging)and neuronal death(as measured by Nissl staining),as well as improvements in sensory and motor functions in rats subjected to middle cerebral artery occlusion.Furthermore,treatment with Lycium barbarum glycopeptide alleviated anxiety and depression-like behaviors and improved memory.Additionally,Lycium barbarum glycopeptide effectively reduced the iron ion content in the ischemic penumbra of the cortex.Moreover,treatment with Lycium barbarum glycopeptide downregulated the expression of ferroptotic and oxidant proteins such as transferrin receptor 1,divalent metal transporter 1,and Acyl-CoA synthetase long-chain family member 4 and upregulated the expression of anti-ferroptotic and antioxidant proteins such as ferroportin 1,solute carrier family 7 member 11,glutathione,and glutathione peroxidase 4.However,these beneficial effects were reversed when ferroptosis was induced with the activator Erastin.Therefore,the positive effects of Lycium barbarum glycopeptide in ischemic stroke are likely mediated through activation of the anti-ferroptotic pathway and the antioxidative System Xc-glutathione-glutathione peroxidase 4 pathway.Overall,our findings highlight the potential use of Lycium barbarum glycopeptide as a neuroprotective agent targeting both ferroptosis and oxidation to decrease ischemic brain damage.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金supported by the China Postdoctoral Science Foundation,No.2022M712689the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB1800029+1 种基金The University Student Innovation Project of Yangzhou University,No.XCX20240856The Jiangsu Provincial Science and Technology Talent Project,No.FZ20240964(all to TX).
文摘Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
基金supported by National Key R&D Program of China (No.2022YFC3501700)National Natural Science Foundation of China (No.82274059)+3 种基金Naval Military Medical University,Far East Talent Project (No.SL-33)Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (No.CPA-Z05-ZC-2024-003)Shanghai Oriental Talent Plan Youth Program (formerly Shanghai Young Top-Notch Talent) (2023)the Baoshan District Medical Key Science (Specialty) and Specialty Brand Construction Project (No.BSZK-2023-A12)。
文摘Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
文摘Objective:To explore the interventional room nursing and its application effects in patients with ischemic stroke treated with tirofiban combined with direct thrombectomy.Methods:A total of 61 patients with ischemic stroke admitted to our hospital from June 2024 to June 2025 were selected and divided into two groups using the red and blue ball method:the control group(n=30,receiving routine interventional room nursing)and the observation group(n=31,receiving additional tirofiban medication-specific nursing+individualized interventional nursing on the basis of routine nursing).The cerebral hemodynamic indicators,adverse reactions,effectiveness of complication nursing,and nursing satisfaction were compared between the two groups.Results:After 7 days of treatment,the observation group had lower cerebrovascular peripheral resistance and higher mean blood flow velocity and mean blood flow volume compared to the control group(all p<0.05).The observation group had a higher effectiveness rate of complication nursing than the control group,with a statistically significant difference(p<0.05).The nursing satisfaction in the observation group(96.77%)was higher than that in the control group(80.00%),with a statistically significant difference(χ^(2)=4.223,p=0.040<0.05).Conclusion:Tirofiban combined with direct thrombectomy can significantly improve cerebral hemodynamics,enhance the effectiveness of complication nursing,and increase patient satisfaction in patients with ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82172546(to XH),82172547(to ZZ)the Natural ScienceFoundation of Guangdong Province,Nos.2023A1515012695(to XH),2024A1515010419(to ZZ)the Science and Technology Plan Project of Guangzhou,Nos.202201020413(to ZZ),2023A04J1099(to ZZ).
文摘White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
文摘BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.
基金National Natural Science Foundation of China,No.82471361(to MZ)the Natural Science Foundation for Excellent Young Scholars of Hunan Province,No.2021JJ20095(to MZ)+3 种基金the Key Research and Development Program of Hunan Province,No.2020SK2063(to MZ)the Research Project on Education and Teaching Innovation of Central South University,No.2021jy145(to MZ)the Natural Science Foundations of Hunan Province,No.2020JJ4134(to MZ)the Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0595(to YP).
文摘Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.
基金supported by the National Natural Science Foundation of China,specifically through grants(No.8227431382304947)Key Research and Development Project of Shaanxi Province(2023GHZD43).Peer re v iew information。
文摘Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.
