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
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
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
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
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
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
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
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
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
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
In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Re...In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Research(Wang et al.,2019),there are some errors in selecting the appropriate images in Figures 4A,4B,and 5A by authors during assembling the images.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 Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perfor...BACKGROUND Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perform a systematic review and meta-analysis on the association of neu-trophil-to-lymphocyte ratio(NLR)and HE in ICH.A secondary outcome exa-mined was the association of NLR and perihematomal(PHE)growth.METHODS Three databases were searched(PubMed,EMBASE,and Cochrane)for studies evaluating the effect of NLR on HE and PHE growth.The inverse variance me-thod was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies’estimates of the logarithm odds ratio(OR).Given heterogeneity of the studies,a random effect was applied.Risk of bias was analyzed using the Newcastle-Ottawa Scale.The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines.The protocol was registered in PROSPERO(No.CRD42024549924).RESULTS Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis.Among those,HE was investigated in eight studies,whereas PHE growth was evaluated in three.Blood sample was obtained on admission in ten studies,and at 24 hours in one study.There was no consensus on cut-off value among the studies.NLR was found to be significantly associated with higher odds of HE(OR=1.09,95%CI:1.04-1.15,I2=86%,P<0.01),and PHE growth(OR=1.28,95%CI:1.19-1.38,I2=0%,P<0.01).Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.CONCLUSION The available literature suggests that a possible association may exist between NLR on admission and HE,and PHE growth.Future studies controlled for systemic confounders should be designed to consolidate this finding.If confirmed,NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.展开更多
As a severe neurological disease,cerebral hemorrhage is dangerous and progresses rapidly,with high disability and fatality rates.Its occurrence seriously harms patients’lives and health,and also causes a heavy social...As a severe neurological disease,cerebral hemorrhage is dangerous and progresses rapidly,with high disability and fatality rates.Its occurrence seriously harms patients’lives and health,and also causes a heavy social burden.Timely diagnosis and treatment of cerebral hemorrhage are essential for improving patients’prognosis.This article reviews the research progress in emergency treatment for patients with cerebral hemorrhage,providing a basis for diagnosis and treatment.展开更多
BACKGROUND Subarachnoid hemorrhage(SAH)is associated with high incidence of anxiety and depression disorders(27%-54%and 20%-42%,respectively),significantly affecting patient quality of life.However,the pathophysiologi...BACKGROUND Subarachnoid hemorrhage(SAH)is associated with high incidence of anxiety and depression disorders(27%-54%and 20%-42%,respectively),significantly affecting patient quality of life.However,the pathophysiological mechanisms underlying post-SAH emotional disorders remain poorly understood,limiting targeted therapeutic interventions.AIM To identify potential biomarkers and therapeutic targets through comprehensive analysis of behavioral,neuroimaging,and inflammatory parameters in a rat SAH model.METHODS We established a rat SAH model using cisternal injection of autologous blood and conducted comprehensive assessments including behavioral tests(elevated plus maze,forced swimming test,sucrose preference test),diffusion tensor imaging(DTI),and inflammatory factor detection.Seventy-two male SD rats were randomly divided into sham and SAH groups,with evaluations performed at multiple time points(1 hour to 72 hours post-hemorrhage).DTI parameters including fractional anisotropy(FA)and apparent diffusion coefficient were measured in limbic-prefrontal circuits.Serum and cerebrospinal fluid inflammatory markers[interleukin-6(IL-6),IL-1β,tumor necrosis factor-α]were quantified using enzyme-linked immunosorbent assay.RESULTS SAH rats exhibited significant anxiety-like and depression-like behaviors at 12 hours,which further deteriorated at 24 hours(open arm time:30.3±4.7 seconds vs 82.1±8.3 seconds in controls,P<0.01;immobility time:136.5±12.7 seconds vs 78.3±9.2 seconds in controls,P<0.01).DTI analysis revealed progressive white matter microstructural damage,with hippocampus-prefrontal FA values decreasing by 21.8%and amygdala-prefrontal FA values by 20.3%at 24 hours(P<0.001).Apparent diffusion coefficient values significantly decreased at 12 hours,indicating cellular edema.Inflammatory markers showed marked elevation,with stronger correlations between cerebrospinal fluid IL-1βand behavioral changes(r=0.72-0.81,P<0.001).CONCLUSION This study demonstrates that post-SAH emotional disorders result from a temporal cascade involving early neuroinflammation and progressive limbic-prefrontal circuit microstructural damage.展开更多
The high mortality and disability rates associated with spontaneous intracerebral hemorrhage(sICH)are primarily attributed to secondary injuries caused by hematoma expansion from continuous bleeding or rehemorrhage.Ra...The high mortality and disability rates associated with spontaneous intracerebral hemorrhage(sICH)are primarily attributed to secondary injuries caused by hematoma expansion from continuous bleeding or rehemorrhage.Rapid hemostasis to prevent hematoma progression is critical in clinical emergencies for improving surgical outcomes and patient prognosis.For internal hemorrhages inaccessible to external interventions,especially for sICH,intravenous hemostatic strategies are essential regardless of ultimate surgical eligibility.This study reported a stealth hemostatic anchor system based on peptide-drug conjugates.Tranexamic acid(TXA),a clinically approved antifibrinolytic agent,served as the hemostatic component,while a von Willebrand factor(vMF)-binding peptide(VBP)enabled targeted delivery by specifically binding to(vMF)exposed at vascular injury sites.A plasmin-cleavable linker was incorporated to control TXA release,ensuring site-specific drug activation.The plasmin-responsive peptide-drug conjugate(RPDC)was synthesized by covalently linking TXA to VBP via the plasmin-cleavable linker.In vitro and in vivo experiments verified the targeted hemostatic efficacy of RPDC,especially demonstrating 42%reduction in hematoma volume(P<0.001 vs.saline;P<0.05 vs.free TXA)with mitigated peri-hematomal pathology in the collagenase-induced ICR mouse ICH model.These results highlight the potential of the stealth hemostatic anchor as a precision therapeutic strategy for managing sICH,particularly in cases of internal hemorrhages inaccessible to surgical intervention or visual inspection.The plasmin-dependent targeting mechanism enables precise drug localization at cryptic hemorrhage sites,but further studies in larger animal models are needed to confirm its efficacy.This design offers a theoretical framework for advancing emergency interventions in cerebral hemorrhage and addressing challenges related to inaccessible bleeding sites.展开更多
BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and iden...BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and identify mortality risk factors.AIM To conduct a single-center retrospective study of 88 patients with delayed PPH to systematically evaluate the clinical efficacy of endovascular treatment,identify independent risk factors for six-month mortality,and propose and validate a predictive model for individualized management of high-risk patients.METHODS This retrospective analysis included 88 patients with delayed PPH treated by endovascular intervention.Patients were stratified into survival(n=64)and mortality(n=24)groups.Clinical and procedural variables were assessed using univariate and multivariate logistic regression.Significant predictors were incorporated into a prognostic nomogram.Model performance was assessed through discrimination(area under the receiver operating characteristic curve),calibration,and decision curve analysis.RESULTS Technical and clinical success rates were 92.0%and 60.2%,respectively.The overall six-month mortality rate was 27.3%(24/88).Independent predictors of mortality included advanced age,prolonged operative time,shorter hospital stay,intra-abdominal infection,coagulation dysfunction,common hepatic artery bleeding,and failure to achieve clinical success.The nomogram demonstrated excellent discrimination(area under the receiver operating characteristic curve=0.943),with good calibration and favorable net benefit on decision curve analysis.CONCLUSION We proposed and validated a predictive nomogram for six-month mortality following endovascular treatment for delayed PPH.The model facilitates individualized risk stratification and may guide clinical decision-making.Early identification of high-risk patients-particularly older individuals or those with infection or coagulopathy-and prompt,personalized intervention may improve outcomes in this high-risk population.展开更多
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.
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 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.
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.
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 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.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 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 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.
文摘In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Research(Wang et al.,2019),there are some errors in selecting the appropriate images in Figures 4A,4B,and 5A by authors during assembling the images.
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.
文摘BACKGROUND Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perform a systematic review and meta-analysis on the association of neu-trophil-to-lymphocyte ratio(NLR)and HE in ICH.A secondary outcome exa-mined was the association of NLR and perihematomal(PHE)growth.METHODS Three databases were searched(PubMed,EMBASE,and Cochrane)for studies evaluating the effect of NLR on HE and PHE growth.The inverse variance me-thod was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies’estimates of the logarithm odds ratio(OR).Given heterogeneity of the studies,a random effect was applied.Risk of bias was analyzed using the Newcastle-Ottawa Scale.The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines.The protocol was registered in PROSPERO(No.CRD42024549924).RESULTS Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis.Among those,HE was investigated in eight studies,whereas PHE growth was evaluated in three.Blood sample was obtained on admission in ten studies,and at 24 hours in one study.There was no consensus on cut-off value among the studies.NLR was found to be significantly associated with higher odds of HE(OR=1.09,95%CI:1.04-1.15,I2=86%,P<0.01),and PHE growth(OR=1.28,95%CI:1.19-1.38,I2=0%,P<0.01).Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.CONCLUSION The available literature suggests that a possible association may exist between NLR on admission and HE,and PHE growth.Future studies controlled for systemic confounders should be designed to consolidate this finding.If confirmed,NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.
文摘As a severe neurological disease,cerebral hemorrhage is dangerous and progresses rapidly,with high disability and fatality rates.Its occurrence seriously harms patients’lives and health,and also causes a heavy social burden.Timely diagnosis and treatment of cerebral hemorrhage are essential for improving patients’prognosis.This article reviews the research progress in emergency treatment for patients with cerebral hemorrhage,providing a basis for diagnosis and treatment.
基金Supported by Clinical Medicine Research and Translational Project of Anhui Province,No.202204295107020036 and No.202304295107020076the Science and Technology Innovation Guidance Project of Bengbu City,No.20200338.
文摘BACKGROUND Subarachnoid hemorrhage(SAH)is associated with high incidence of anxiety and depression disorders(27%-54%and 20%-42%,respectively),significantly affecting patient quality of life.However,the pathophysiological mechanisms underlying post-SAH emotional disorders remain poorly understood,limiting targeted therapeutic interventions.AIM To identify potential biomarkers and therapeutic targets through comprehensive analysis of behavioral,neuroimaging,and inflammatory parameters in a rat SAH model.METHODS We established a rat SAH model using cisternal injection of autologous blood and conducted comprehensive assessments including behavioral tests(elevated plus maze,forced swimming test,sucrose preference test),diffusion tensor imaging(DTI),and inflammatory factor detection.Seventy-two male SD rats were randomly divided into sham and SAH groups,with evaluations performed at multiple time points(1 hour to 72 hours post-hemorrhage).DTI parameters including fractional anisotropy(FA)and apparent diffusion coefficient were measured in limbic-prefrontal circuits.Serum and cerebrospinal fluid inflammatory markers[interleukin-6(IL-6),IL-1β,tumor necrosis factor-α]were quantified using enzyme-linked immunosorbent assay.RESULTS SAH rats exhibited significant anxiety-like and depression-like behaviors at 12 hours,which further deteriorated at 24 hours(open arm time:30.3±4.7 seconds vs 82.1±8.3 seconds in controls,P<0.01;immobility time:136.5±12.7 seconds vs 78.3±9.2 seconds in controls,P<0.01).DTI analysis revealed progressive white matter microstructural damage,with hippocampus-prefrontal FA values decreasing by 21.8%and amygdala-prefrontal FA values by 20.3%at 24 hours(P<0.001).Apparent diffusion coefficient values significantly decreased at 12 hours,indicating cellular edema.Inflammatory markers showed marked elevation,with stronger correlations between cerebrospinal fluid IL-1βand behavioral changes(r=0.72-0.81,P<0.001).CONCLUSION This study demonstrates that post-SAH emotional disorders result from a temporal cascade involving early neuroinflammation and progressive limbic-prefrontal circuit microstructural damage.
基金support of the Guizhou Provincial Postdoctoral Research Initiation Fund (BSH-Q-2023-10)Startup Fund for High-Level Talent Research at Guizhou Medical University (26232020159)+4 种基金the High-level Innovation Talents (No. GCC[2023]048)the Guizhou Provincial Scientific and Technologic Innovation Base ([2023]003)National Natural Science Foundation Cultivation Project of Guizhou Medical University Affiliated Hospital (gyfynsfc[2022]-1)Key lab of acute brain injury and function repair in Guizhou Medical University ([2024]fy007)the support from the Laboratory Animal Engineering Technology Center of Guizhou Province。
文摘The high mortality and disability rates associated with spontaneous intracerebral hemorrhage(sICH)are primarily attributed to secondary injuries caused by hematoma expansion from continuous bleeding or rehemorrhage.Rapid hemostasis to prevent hematoma progression is critical in clinical emergencies for improving surgical outcomes and patient prognosis.For internal hemorrhages inaccessible to external interventions,especially for sICH,intravenous hemostatic strategies are essential regardless of ultimate surgical eligibility.This study reported a stealth hemostatic anchor system based on peptide-drug conjugates.Tranexamic acid(TXA),a clinically approved antifibrinolytic agent,served as the hemostatic component,while a von Willebrand factor(vMF)-binding peptide(VBP)enabled targeted delivery by specifically binding to(vMF)exposed at vascular injury sites.A plasmin-cleavable linker was incorporated to control TXA release,ensuring site-specific drug activation.The plasmin-responsive peptide-drug conjugate(RPDC)was synthesized by covalently linking TXA to VBP via the plasmin-cleavable linker.In vitro and in vivo experiments verified the targeted hemostatic efficacy of RPDC,especially demonstrating 42%reduction in hematoma volume(P<0.001 vs.saline;P<0.05 vs.free TXA)with mitigated peri-hematomal pathology in the collagenase-induced ICR mouse ICH model.These results highlight the potential of the stealth hemostatic anchor as a precision therapeutic strategy for managing sICH,particularly in cases of internal hemorrhages inaccessible to surgical intervention or visual inspection.The plasmin-dependent targeting mechanism enables precise drug localization at cryptic hemorrhage sites,but further studies in larger animal models are needed to confirm its efficacy.This design offers a theoretical framework for advancing emergency interventions in cerebral hemorrhage and addressing challenges related to inaccessible bleeding sites.
文摘BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and identify mortality risk factors.AIM To conduct a single-center retrospective study of 88 patients with delayed PPH to systematically evaluate the clinical efficacy of endovascular treatment,identify independent risk factors for six-month mortality,and propose and validate a predictive model for individualized management of high-risk patients.METHODS This retrospective analysis included 88 patients with delayed PPH treated by endovascular intervention.Patients were stratified into survival(n=64)and mortality(n=24)groups.Clinical and procedural variables were assessed using univariate and multivariate logistic regression.Significant predictors were incorporated into a prognostic nomogram.Model performance was assessed through discrimination(area under the receiver operating characteristic curve),calibration,and decision curve analysis.RESULTS Technical and clinical success rates were 92.0%and 60.2%,respectively.The overall six-month mortality rate was 27.3%(24/88).Independent predictors of mortality included advanced age,prolonged operative time,shorter hospital stay,intra-abdominal infection,coagulation dysfunction,common hepatic artery bleeding,and failure to achieve clinical success.The nomogram demonstrated excellent discrimination(area under the receiver operating characteristic curve=0.943),with good calibration and favorable net benefit on decision curve analysis.CONCLUSION We proposed and validated a predictive nomogram for six-month mortality following endovascular treatment for delayed PPH.The model facilitates individualized risk stratification and may guide clinical decision-making.Early identification of high-risk patients-particularly older individuals or those with infection or coagulopathy-and prompt,personalized intervention may improve outcomes in this high-risk population.
