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
This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.L...This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.展开更多
Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction...Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.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
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
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
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 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
BACKGROUND Aneurysmal subarachnoid hemorrhage(aSAH),a particularly devastating subtype of stroke,is associated with substantial rates of mortality and long-term functional impairment.Despite notable progress in therap...BACKGROUND Aneurysmal subarachnoid hemorrhage(aSAH),a particularly devastating subtype of stroke,is associated with substantial rates of mortality and long-term functional impairment.Despite notable progress in therapeutic strategies,a considerable proportion of aSAH survivors continue to suffer from neuropsychiatric complications,most commonly anxiety and depression,which detrimentally impact their overall quality of life.AIM To investigate the prevalence of anxiety and depressive symptoms in patients with aSAH and to identify associated clinical risk factors.METHODS Clinical records of 1268 consecutive patients diagnosed with aSAH and treated between 2016 and 2022 were retrospectively reviewed.At follow-up,psychological assessments were performed using the Hospital Anxiety and Depression Scale to quantify symptoms of anxiety and depression.To identify independent predictors associated with these psychological outcomes post-aSAH,both univariate and multivariate statistical analyses were employed.RESULTS Among the studied cohort,34.9%of patients presented with anxiety symptoms,while 31.8%demonstrated depressive features.Multivariate analysis identified female sex,presence of multiple aneurysms,a positive family history of cerebral hemorrhage,and receiving surgical clipping as independent predictors of anxiety.In contrast,significant predictors of depression included female sex,multiplicity of aneurysms,posterior circulation aneurysm localization,and poor clinical outcome.Notably,age above 60 years and documented functional recovery were associated with a reduced risk of depression.CONCLUSION Anxiety and depression are common neuropsychiatric sequelae in survivors of aSAH,each associated with a distinct set of risk factors.Early identification and targeted management of these risk profiles may facilitate more effective intervention strategies for psychological comorbidities,ultimately contributing to improved long-term patient outcomes.展开更多
Retraction Note to:Neurosci.Bull.(2019)35:461-470 https://doi.org/10.1007/s12264-018-00333-w The Editor-in-Chief has retracted this article.After publication,concerns were raised regarding image similarities across pu...Retraction Note to:Neurosci.Bull.(2019)35:461-470 https://doi.org/10.1007/s12264-018-00333-w The Editor-in-Chief has retracted this article.After publication,concerns were raised regarding image similarities across publications from unrelated authors.Specifically.展开更多
The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unab...The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unable to provide a satisfactory explanation and raw data for the concerns upon request.展开更多
Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying ...Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.展开更多
The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions...The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions,but its role in early brain injury(EBI)after SAH remains unclear.In this study,we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms.WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue,correlating negatively with microglial activation.AAV-WNK1 alleviated brain edema,neuronal necrosis,behavioral deficits,and inflammation by inhibiting NLRP3 inflammasome activation.In hemin-stimulated BV-2 cells,WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines.Chloride counteracted WNK1’s inhibitory effects,and WNK1 suppressed P2X7R-induced NLRP3 activation.Mechanistically,WNK1 functioned via the OXSR1/STK39 pathway.These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation,presenting a potential therapeutic target for SAH treatment.展开更多
Background:Subarachnoid hemorrhage(SAH)is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery.This study aimed to investigate the epidemiological characteristics of SAH betwe...Background:Subarachnoid hemorrhage(SAH)is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery.This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.Methods:Data on SAH incidence,mortality,and disability-adjusted life-years(DALYs)from 1990 to 2021 were obtained from the Global Burden of Disease Study(GBD)2021.Estimated annual percentage changes(EAPCs)were calculated to evaluate changes in the age-standardized rate(ASR)of incidence and mortality,as well as trends in SAH burden.The relationship between disease burden and socio-demographic index(SDI)was also analyzed.Results:In 2021,the incidence of SAH was found to be 37.09%higher than that in 1990;however,the age-standardized incidence rates(ASIRs)showed a decreased[EAPC:-1.52;95%uncertainty interval(UI)-1.66 to-1.37].Furthermore,both the number and rates of deaths and DALYs decreased over time.It was observed that females had lower rates compared to males.Among all regions,the high-income Asia Pacific region exhibited the highest ASIR(14.09/100,000;95%UI 12.30/100,000-16.39/100,000)in 2021,with an EPAC for ASIR<0 indicating decreasing trend over time for SAH ASIR.Oceania recorded the highest age-standardized mortality rates(ASMRs)and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61(95%UI 6.03-11.95)and 285.62(95%UI 209.42-379.65).The burden associated with SAH primarily affected individuals aged between 50-69 years old.Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.Conclusions:The burden of SAH varies by gender,age group,and geographical region.Although the ASRs have shown a decline over time,the burden of SAH remains significant,especially in regions with middle and low-middle SDI levels.High systolic blood pressure stands out as a key risk factor for SAH.More specific supportive measures are necessary to alleviate the global burden of SAH.展开更多
Objective To study the expression change of interleukin-8 （IL-8） gene in the basilar artery of rabbit and the effect of IL-8 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage ...Objective To study the expression change of interleukin-8 （IL-8） gene in the basilar artery of rabbit and the effect of IL-8 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage （SAH）. Methods Thirty five healthy Japanese White Rabbits were randomly divided into saline-control group and experimental group. The experimental group was subdivided into four groups, representing day 1, 4, 7 and 14 after the first blood injection of SAH. The delayed cerebral vasospasm （DCVS） model was established by double injection of autologous blood into the cisterna magna. The expression change of cytokine IL-8 mRNA in the basilar artery was analyzed by RT- PCR. Results The expression of IL-8 gene increased on day 4-7 after the first blood injection of SAH compared with control （P 〈 0.001）, and decreased to normal on day 14. The expression of IL-8 gene in the SAH groups were positively correlated with the degree of basilar artery stenosis （r = 0.642, P 〈 0.01）. Conclusion The expression level of IL-8 gene in basilar arteries was intimately associated with the degree of cerebral vasospasm, suggesting that IL-8 may play an important role in the DCVS after SAH as an immunological inflammatory factor.展开更多
In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can re- lieve glaucomatous optic neuropathy. Increased intracranial pressure can also r...In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can re- lieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22-30 years （12 females and 3 males）, at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg （1 mmHg = 0.133 kPa）, then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ＋ 0.1 mm （range： 0.77-1.05 mm）, 0.77 ＋ 0.11 mm （range： 0.60-0.94 mm）, 0.70 ＋ 0.08 mm （range： 0.62-0.80 ram）, and 0.68 _＋ 0.08 mm （range： 0.57-0.77 mm） at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased in- tra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry （registration number： ChiCTR-ONRC-14004947）.展开更多
BACKGROUND Nontraumatic convexal subarachnoid hemorrhage(c SAH)is a rare type of atypical subarachnoid hemorrhage.It mainly presents as a focal and transient neurological deficit with similar manifestations as transie...BACKGROUND Nontraumatic convexal subarachnoid hemorrhage(c SAH)is a rare type of atypical subarachnoid hemorrhage.It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack.CASE SUMMARY We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study.Computed tomography examination indicated a high-density image of the right frontalparietal sulcus.Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction(stenosis rate approximately 70%).CONCLUSION The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of c SAH.展开更多
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this ...Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin(100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca2+ overload.Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2–related factor2, heme oxygenase-1, phospho-Akt and B-cell lymphoma2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.展开更多
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ...Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.展开更多
Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evalua...Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.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National Nature Science Foundation of China,No.81870944(to FL).
文摘This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.
基金National Natural Science Foundation of China,No.81901336(to JM).
文摘Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.
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.
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 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Supported by Shenzhen Medical Academy of Research and Translation Program,No.A2302031.
文摘BACKGROUND Aneurysmal subarachnoid hemorrhage(aSAH),a particularly devastating subtype of stroke,is associated with substantial rates of mortality and long-term functional impairment.Despite notable progress in therapeutic strategies,a considerable proportion of aSAH survivors continue to suffer from neuropsychiatric complications,most commonly anxiety and depression,which detrimentally impact their overall quality of life.AIM To investigate the prevalence of anxiety and depressive symptoms in patients with aSAH and to identify associated clinical risk factors.METHODS Clinical records of 1268 consecutive patients diagnosed with aSAH and treated between 2016 and 2022 were retrospectively reviewed.At follow-up,psychological assessments were performed using the Hospital Anxiety and Depression Scale to quantify symptoms of anxiety and depression.To identify independent predictors associated with these psychological outcomes post-aSAH,both univariate and multivariate statistical analyses were employed.RESULTS Among the studied cohort,34.9%of patients presented with anxiety symptoms,while 31.8%demonstrated depressive features.Multivariate analysis identified female sex,presence of multiple aneurysms,a positive family history of cerebral hemorrhage,and receiving surgical clipping as independent predictors of anxiety.In contrast,significant predictors of depression included female sex,multiplicity of aneurysms,posterior circulation aneurysm localization,and poor clinical outcome.Notably,age above 60 years and documented functional recovery were associated with a reduced risk of depression.CONCLUSION Anxiety and depression are common neuropsychiatric sequelae in survivors of aSAH,each associated with a distinct set of risk factors.Early identification and targeted management of these risk profiles may facilitate more effective intervention strategies for psychological comorbidities,ultimately contributing to improved long-term patient outcomes.
文摘Retraction Note to:Neurosci.Bull.(2019)35:461-470 https://doi.org/10.1007/s12264-018-00333-w The Editor-in-Chief has retracted this article.After publication,concerns were raised regarding image similarities across publications from unrelated authors.Specifically.
文摘The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unable to provide a satisfactory explanation and raw data for the concerns upon request.
基金supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science KAKENHI 22K09110.
文摘Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.
基金supported by Grants from the Basic Research Program of Jiangsu(BK20240492)Lianyungang Science and Technology Plan Project(JCYJ2304)+2 种基金Lianyungang Aging Health Research Project(L202301)Doctoral Research Start-up Fund of the First Peopel’Hospital of Lianyungang City(BS202314)The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions,but its role in early brain injury(EBI)after SAH remains unclear.In this study,we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms.WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue,correlating negatively with microglial activation.AAV-WNK1 alleviated brain edema,neuronal necrosis,behavioral deficits,and inflammation by inhibiting NLRP3 inflammasome activation.In hemin-stimulated BV-2 cells,WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines.Chloride counteracted WNK1’s inhibitory effects,and WNK1 suppressed P2X7R-induced NLRP3 activation.Mechanistically,WNK1 functioned via the OXSR1/STK39 pathway.These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation,presenting a potential therapeutic target for SAH treatment.
文摘Background:Subarachnoid hemorrhage(SAH)is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery.This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.Methods:Data on SAH incidence,mortality,and disability-adjusted life-years(DALYs)from 1990 to 2021 were obtained from the Global Burden of Disease Study(GBD)2021.Estimated annual percentage changes(EAPCs)were calculated to evaluate changes in the age-standardized rate(ASR)of incidence and mortality,as well as trends in SAH burden.The relationship between disease burden and socio-demographic index(SDI)was also analyzed.Results:In 2021,the incidence of SAH was found to be 37.09%higher than that in 1990;however,the age-standardized incidence rates(ASIRs)showed a decreased[EAPC:-1.52;95%uncertainty interval(UI)-1.66 to-1.37].Furthermore,both the number and rates of deaths and DALYs decreased over time.It was observed that females had lower rates compared to males.Among all regions,the high-income Asia Pacific region exhibited the highest ASIR(14.09/100,000;95%UI 12.30/100,000-16.39/100,000)in 2021,with an EPAC for ASIR<0 indicating decreasing trend over time for SAH ASIR.Oceania recorded the highest age-standardized mortality rates(ASMRs)and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61(95%UI 6.03-11.95)and 285.62(95%UI 209.42-379.65).The burden associated with SAH primarily affected individuals aged between 50-69 years old.Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.Conclusions:The burden of SAH varies by gender,age group,and geographical region.Although the ASRs have shown a decline over time,the burden of SAH remains significant,especially in regions with middle and low-middle SDI levels.High systolic blood pressure stands out as a key risk factor for SAH.More specific supportive measures are necessary to alleviate the global burden of SAH.
文摘Objective To study the expression change of interleukin-8 （IL-8） gene in the basilar artery of rabbit and the effect of IL-8 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage （SAH）. Methods Thirty five healthy Japanese White Rabbits were randomly divided into saline-control group and experimental group. The experimental group was subdivided into four groups, representing day 1, 4, 7 and 14 after the first blood injection of SAH. The delayed cerebral vasospasm （DCVS） model was established by double injection of autologous blood into the cisterna magna. The expression change of cytokine IL-8 mRNA in the basilar artery was analyzed by RT- PCR. Results The expression of IL-8 gene increased on day 4-7 after the first blood injection of SAH compared with control （P 〈 0.001）, and decreased to normal on day 14. The expression of IL-8 gene in the SAH groups were positively correlated with the degree of basilar artery stenosis （r = 0.642, P 〈 0.01）. Conclusion The expression level of IL-8 gene in basilar arteries was intimately associated with the degree of cerebral vasospasm, suggesting that IL-8 may play an important role in the DCVS after SAH as an immunological inflammatory factor.
文摘In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can re- lieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22-30 years （12 females and 3 males）, at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg （1 mmHg = 0.133 kPa）, then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ＋ 0.1 mm （range： 0.77-1.05 mm）, 0.77 ＋ 0.11 mm （range： 0.60-0.94 mm）, 0.70 ＋ 0.08 mm （range： 0.62-0.80 ram）, and 0.68 _＋ 0.08 mm （range： 0.57-0.77 mm） at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased in- tra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry （registration number： ChiCTR-ONRC-14004947）.
基金Supported by Research Fund of the Department of Science and Technology of Shandong Province,China,No.2019WS328。
文摘BACKGROUND Nontraumatic convexal subarachnoid hemorrhage(c SAH)is a rare type of atypical subarachnoid hemorrhage.It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack.CASE SUMMARY We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study.Computed tomography examination indicated a high-density image of the right frontalparietal sulcus.Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction(stenosis rate approximately 70%).CONCLUSION The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of c SAH.
基金supported by funds from the Project of Medical and Health Technology Development Program in Shandong Province,China(2016WS0196)
文摘Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin(100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca2+ overload.Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2–related factor2, heme oxygenase-1, phospho-Akt and B-cell lymphoma2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
基金supported by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science(grant number:17K10825)to HS
文摘Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China (81601938)the Natural Science Fund of Shaanxi Province (2016JQ8010)the Science and Technology Projects Fund of Xi’an city (2016050SF/YX06(6))
文摘Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
