Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strate...Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strategies for clinical nursing.Methods:Eighty patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2023 to June 2025 were selected and randomly divided into an observation group(n=40,receiving systematic stepwise rehabilitation nursing)and a control group(n=40,receiving conventional nursing).The intervention effects were analyzed by comparing changes in the National Institutes of Health Stroke Scale(NIHSS)scores for neurological recovery,Short Form 36 Health Survey(SF-36)scores for quality of life,Exercise of Self-Care Agency Scale(ESCA)scores for self-management ability,compliance,and the Mishel Uncertainty in Illness Scale(MUIS)scores between the two groups.Results:All scores in the observation group were significantly better than those in the control group after the intervention(p<0.05).Specifically,the NIHSS scores decreased more significantly,the total SF-36 scores increased,the ESCA scores increased significantly,while the MUIS scores decreased significantly,and compliance improved markedly,indicating a reduction in disease uncertainty among patients.Conclusion:Systematic stepwise rehabilitation nursing intervention can significantly improve neurological recovery,quality of life,self-management ability,and compliance in patients with hypertensive intracerebral hemorrhage,while effectively reducing disease uncertainty.It is worthy of clinical promotion and application.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and...AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain in...Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.展开更多
Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority ...Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).展开更多
In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause o...In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.展开更多
Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to mode...Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.展开更多
Dear Editor,We present the reported case of repetitive bilateral suprachoroidal expulsive hemorrhage(SEH)after anti-glaucoma surgeries.SEH is a rare but potentially devastating complication of intraocular surgery.Long...Dear Editor,We present the reported case of repetitive bilateral suprachoroidal expulsive hemorrhage(SEH)after anti-glaucoma surgeries.SEH is a rare but potentially devastating complication of intraocular surgery.Long-term ocular hypertension,high myopia,older age,arterial sclerosis,and aphakia have been reported as preoperative risk factors for developing SEH^([1]).The prognosis for the visual acuity is poor without proper management.A suggested time for surgical drainage is said to be 10-14d when the hemorrhagic clot begins to liquefy^([2]).展开更多
Spinal subarachnoid hemorrhage(SSAH)is a relatively uncommon but significant cause of acute and progressive neurological impairment.It represents less than 1.5%of all instances of bleeding within the subarachnoid spac...Spinal subarachnoid hemorrhage(SSAH)is a relatively uncommon but significant cause of acute and progressive neurological impairment.It represents less than 1.5%of all instances of bleeding within the subarachnoid space.[1]The early stages of SSAH often present atypical clinical symptoms,making diagnosis challenging and potentially leading to treatment delays,which further result in irreversible neurological damage.Lower back pain is a common complaint in the emergency department(ED).[2]Common causes include overuse resulting in back strain.展开更多
Objective:To preliminarily construct and apply a longitudinal trajectory model for the prognosis of intracerebral hemorrhage(ICH)based on blood urea nitrogen(BUN)characteristics.Methods:Clinical data from 320 ICH pati...Objective:To preliminarily construct and apply a longitudinal trajectory model for the prognosis of intracerebral hemorrhage(ICH)based on blood urea nitrogen(BUN)characteristics.Methods:Clinical data from 320 ICH patients admitted to our hospital between 2020 and 2024 were collected,including demographic information,National Institutes of Health Stroke Scale(NIHSS)scores at admission,dynamic changes in BUN levels during treatment,and 30-day survival outcomes.A latent class growth model(LCGM)was first used for preliminary modeling,followed by a latent growth mixture modeling(GMM)approach to determine the final model.Three classes of BUN trajectories for ICH prognosis were identified,and latent classes were established.GMM modeling was then performed on these latent classes,considering linear,quadratic,and cubic polynomial forms;six GMM models were constructed and individuals were assigned to latent trajectory groups for validation.Results:LCGM analysis ultimately identified three dynamic BUN trajectory groups:Sustained low-level group(76 cases,23.8%):BUN remained stable between 3.1-9.0 mmol/L,with the highest 30-day survival rate(98.7%).Fluctuating-declining group(222 cases,69.4%):BUN initially increased and then slowly decreased(peak at day 3:15.2 mmol/L),with a 30-day mortality of 8.1%(18/222),higher than the sustained low-level group.Sustained high-level group(22 cases,6.9%):BUN mean>9.0 mmol/L,with a 30-day mortality of 41.7%(P=0.000).GMM model fitting showed that the cubic polynomial GMM model was optimal(AIC=6754.474,BIC=6852.450,Entropy=0.905).Incorporating gender,age,and BMI as covariates revealed significant effects for gender(Estimate=0.045,-0.011,P=0.000,0.000).The AUC for predicting 30-day mortality was 0.88(sensitivity 82.8%,specificity 77.9%),which increased to 0.89 when combined with admission NIHSS scores.Conclusion:The LCGM+GMM model based on dynamic BUN trajectories effectively distinguishes prognostic subgroups in ICH patients.Patients with persistently elevated or fluctuating-rising BUN levels have a significantly higher mortality risk compared to those with sustained low levels.This model provides a new quantitative tool for early identification of high-risk patients and poor prognoses.展开更多
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially...Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.展开更多
BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral...BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.展开更多
Intracerebral hemorrhage(ICH) is a significant and growing threat to human health,with increasing incidence.Promoting blood circulation and removing blood stasis therapy(PBCRBS),a Traditional Chinese Medicine therapy,...Intracerebral hemorrhage(ICH) is a significant and growing threat to human health,with increasing incidence.Promoting blood circulation and removing blood stasis therapy(PBCRBS),a Traditional Chinese Medicine therapy,can be an adjuvant therapy to benefit patients with ICH by improving clinical efficacy.However,in theory,using PBCRBS to treat ICH carries the risk of hematoma enlargement and rebleeding,which has led to controversy over its application in ICH treatment.To demonstrate the effectiveness and safety of PBCRBS in treating ICH,this review first analyzes the pathological and physiological basis of ICH and secondly,the cascade of response after ICH and the involvement of cytokines and signaling pathways in this process.Finally,experimental and clinical studies on the treatment of ICH with PBCRBS over the past decade were retrieved from the Pub Med and China National Knowledge Infrastructure databases,and the content of these studies was used to summarize commonly used herbs with PBCRBS effects and their mechanisms of action.Through analysis,hypertension has been identified as the most common cause of ICH.Heme,interleukin,reactive oxygen species,coagulation promoting particles and other induced mass effects,inflammation,oxidative stress,and coagulation cascade reactions lead to brain damage following ICH.This review includes 56 experimental studies and 83 clinical studies summarizing 28 commonly used herbs,demonstrating the positive impact of PBCRBS as an adjuvant therapy for ICH.In summary,PBCRBS appears effective and safe for treating ICH.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strategies for clinical nursing.Methods:Eighty patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2023 to June 2025 were selected and randomly divided into an observation group(n=40,receiving systematic stepwise rehabilitation nursing)and a control group(n=40,receiving conventional nursing).The intervention effects were analyzed by comparing changes in the National Institutes of Health Stroke Scale(NIHSS)scores for neurological recovery,Short Form 36 Health Survey(SF-36)scores for quality of life,Exercise of Self-Care Agency Scale(ESCA)scores for self-management ability,compliance,and the Mishel Uncertainty in Illness Scale(MUIS)scores between the two groups.Results:All scores in the observation group were significantly better than those in the control group after the intervention(p<0.05).Specifically,the NIHSS scores decreased more significantly,the total SF-36 scores increased,the ESCA scores increased significantly,while the MUIS scores decreased significantly,and compliance improved markedly,indicating a reduction in disease uncertainty among patients.Conclusion:Systematic stepwise rehabilitation nursing intervention can significantly improve neurological recovery,quality of life,self-management ability,and compliance in patients with hypertensive intracerebral hemorrhage,while effectively reducing disease uncertainty.It is worthy of clinical promotion and application.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(No.2025ZR172).
文摘AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金supported by the National Natural Science Foundation of China,No.81870927(to ZH)the Natural Science Foundation Project ofChongqing Science and Technology Commission,No.CSTB2023NSCQ-MSX0112(to ZH).
文摘Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.
文摘Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).
文摘In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.
基金Natural Science Foundation of Hubei Province,Grant/Award Number:2024AFB877the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science&Technology Bureau),Grant/Award Number:2023GGXM003+3 种基金Chongqing Municipal Health Commission,Grant/Award Number:YXGD202451Organization Department of Chongqing Municipal Party Committee,Grant/Award Number:cstc2024ycjh-bgzxm0103National Natural Science Foundation of China,Grant/Award Number:82371361Jingmen Science and Technology Bureau,Grant/Award Number:2024ZDYF012。
文摘Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.
基金Supported by National Natural Science Foundation of China(No.82171087No.82201228)+1 种基金Natural Science Foundation of Hunan Province(No.2024JJ6570)the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University.
文摘Dear Editor,We present the reported case of repetitive bilateral suprachoroidal expulsive hemorrhage(SEH)after anti-glaucoma surgeries.SEH is a rare but potentially devastating complication of intraocular surgery.Long-term ocular hypertension,high myopia,older age,arterial sclerosis,and aphakia have been reported as preoperative risk factors for developing SEH^([1]).The prognosis for the visual acuity is poor without proper management.A suggested time for surgical drainage is said to be 10-14d when the hemorrhagic clot begins to liquefy^([2]).
基金National Natural Science Foundation of China(82472218)National Key Clinical Specialist Construction Project(Z155080000004)+4 种基金National Key Research and Development Program of China(2024YFC3044400)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0506502)the Science and Technology of Shanghai Committee(23Y31900100)Shen Kang Hospital Development Center Project for Technical Standardization Management and Promotion(SHDC22023239)Key Supporting Discipline of Shanghai Healthcare System(2023ZDFC0102).
文摘Spinal subarachnoid hemorrhage(SSAH)is a relatively uncommon but significant cause of acute and progressive neurological impairment.It represents less than 1.5%of all instances of bleeding within the subarachnoid space.[1]The early stages of SSAH often present atypical clinical symptoms,making diagnosis challenging and potentially leading to treatment delays,which further result in irreversible neurological damage.Lower back pain is a common complaint in the emergency department(ED).[2]Common causes include overuse resulting in back strain.
文摘Objective:To preliminarily construct and apply a longitudinal trajectory model for the prognosis of intracerebral hemorrhage(ICH)based on blood urea nitrogen(BUN)characteristics.Methods:Clinical data from 320 ICH patients admitted to our hospital between 2020 and 2024 were collected,including demographic information,National Institutes of Health Stroke Scale(NIHSS)scores at admission,dynamic changes in BUN levels during treatment,and 30-day survival outcomes.A latent class growth model(LCGM)was first used for preliminary modeling,followed by a latent growth mixture modeling(GMM)approach to determine the final model.Three classes of BUN trajectories for ICH prognosis were identified,and latent classes were established.GMM modeling was then performed on these latent classes,considering linear,quadratic,and cubic polynomial forms;six GMM models were constructed and individuals were assigned to latent trajectory groups for validation.Results:LCGM analysis ultimately identified three dynamic BUN trajectory groups:Sustained low-level group(76 cases,23.8%):BUN remained stable between 3.1-9.0 mmol/L,with the highest 30-day survival rate(98.7%).Fluctuating-declining group(222 cases,69.4%):BUN initially increased and then slowly decreased(peak at day 3:15.2 mmol/L),with a 30-day mortality of 8.1%(18/222),higher than the sustained low-level group.Sustained high-level group(22 cases,6.9%):BUN mean>9.0 mmol/L,with a 30-day mortality of 41.7%(P=0.000).GMM model fitting showed that the cubic polynomial GMM model was optimal(AIC=6754.474,BIC=6852.450,Entropy=0.905).Incorporating gender,age,and BMI as covariates revealed significant effects for gender(Estimate=0.045,-0.011,P=0.000,0.000).The AUC for predicting 30-day mortality was 0.88(sensitivity 82.8%,specificity 77.9%),which increased to 0.89 when combined with admission NIHSS scores.Conclusion:The LCGM+GMM model based on dynamic BUN trajectories effectively distinguishes prognostic subgroups in ICH patients.Patients with persistently elevated or fluctuating-rising BUN levels have a significantly higher mortality risk compared to those with sustained low levels.This model provides a new quantitative tool for early identification of high-risk patients and poor prognoses.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
基金Supported by Shanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02Doctor Foundation of the Second Affiliated Hospital of Xi’an Medical University,No.X2Y-R11.
文摘Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.
基金Supported by the Shaanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02.
文摘BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.
基金National Natural Science Foundation of China:Study on the Intervention Mechanism of Zhilong Huoxue Tongyu Capsule in Hypertensive Myocardial Fibrosis by Regulating Transforming Growth Factor-β/Smad3/Erbb4-IR/miR29b Loop (No.82074378)Project of Science & Technology Department of Sichuan Province:Research on the Optimization of Basic and Clinical Plans for Treating Coronary Heart Disease and Heart Failure based on Xuanfu Theory (No.2022YFS0618)+1 种基金Luzhou Science and Technology Bureau Project:the Mechanism of Hirudin Inhibiting AngⅡInduced Myocardial Hypertrophy by Regulating Autophagy and NOD-like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome (No.2023JYJ029)Southwest Medical University Project:Study on the Mechanism of Zhilong Huoxue Tongyu Capsules in Improving NOD-like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome Mediated Cardiomyocyte Pyroptosis in Heart Failure by Regulating the HippoYes-Associated Protein Pathway (No.2023ZYYQ04)。
文摘Intracerebral hemorrhage(ICH) is a significant and growing threat to human health,with increasing incidence.Promoting blood circulation and removing blood stasis therapy(PBCRBS),a Traditional Chinese Medicine therapy,can be an adjuvant therapy to benefit patients with ICH by improving clinical efficacy.However,in theory,using PBCRBS to treat ICH carries the risk of hematoma enlargement and rebleeding,which has led to controversy over its application in ICH treatment.To demonstrate the effectiveness and safety of PBCRBS in treating ICH,this review first analyzes the pathological and physiological basis of ICH and secondly,the cascade of response after ICH and the involvement of cytokines and signaling pathways in this process.Finally,experimental and clinical studies on the treatment of ICH with PBCRBS over the past decade were retrieved from the Pub Med and China National Knowledge Infrastructure databases,and the content of these studies was used to summarize commonly used herbs with PBCRBS effects and their mechanisms of action.Through analysis,hypertension has been identified as the most common cause of ICH.Heme,interleukin,reactive oxygen species,coagulation promoting particles and other induced mass effects,inflammation,oxidative stress,and coagulation cascade reactions lead to brain damage following ICH.This review includes 56 experimental studies and 83 clinical studies summarizing 28 commonly used herbs,demonstrating the positive impact of PBCRBS as an adjuvant therapy for ICH.In summary,PBCRBS appears effective and safe for treating ICH.
