The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct facto...The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.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
The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent...The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.展开更多
BACKGROUND Subarachnoid hemorrhage is a severe neurological condition that requires prompt and appropriate treatment to prevent complications.Aneurysms are the most common cause of spontaneous subarachnoid hemorrhage....BACKGROUND Subarachnoid hemorrhage is a severe neurological condition that requires prompt and appropriate treatment to prevent complications.Aneurysms are the most common cause of spontaneous subarachnoid hemorrhage.Conversely,basilar artery perforator aneurysms(BAPAs)are a rare etiology.There is no consensus on the optimal management of ruptured BAPAs in the acute setting.CASE SUMMARY We present a case series of 3 patients with ruptured BAPAs who were treated at our institution.Two patients had a modified Fisher grade of I,and one had a grade of IV on initial presentation.The aneurysms were detected by computed tomography angiography in two cases and conventional angiography in one case.The 3 patients underwent endovascular treatment with Guglielmi detachable coils.Post-treatment,the patients had good clinical outcomes,and follow-up brain computed tomography scans showed reduced subarachnoid hemorrhage without any new hemorrhage.However,one patient experienced a cerebral infarction 2 months later and eventually succumbed to the condition.The other 2 patients showed progressive recovery,and no aneurysm recurrence was observed at the 2-year follow-up.CONCLUSION Endovascular treatment may be a preferable approach for managing ruptured BAPAs compared with surgical intervention or conservative management.Early detection and prompt treatment is important to achieve favorable patient outcomes.展开更多
Objective:To explore the clinical and pathological characteristics of cerebral venous sinus thrombosis(CVST)with subarachnoid hemorrhage(SAH)and intracerebral hemorrhage(ICH),and to investigate the diagnosis,radiograp...Objective:To explore the clinical and pathological characteristics of cerebral venous sinus thrombosis(CVST)with subarachnoid hemorrhage(SAH)and intracerebral hemorrhage(ICH),and to investigate the diagnosis,radiographic changes,and prognosis over the course of treatment.Methods:The clinical data and radiographic findings of a young male CVST patient,who presented with initial symptoms of SAH and ICH,were collected and analyzed.The relevant literature was also reviewed.Results:The patient had no specific clinical symptoms except for headache.The brain computed tomography(CT)scan revealed SAH,a high-density shadow in the right posterior fossa and cerebellar hemisphere,and ICH in the left frontal lobe.Magnetic resonance venography(MRV)further revealed bilateral thrombosis in the transverse and sigmoid sinuses.Conclusion:CVST with SAH and ICH is rare and difficult to diagnose.Careful radiological study and clinical analysis are important for the correct and early diagnosis of this condition.Anticoagulation therapy is considered the primary treatment for CVST.展开更多
Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro...Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.展开更多
Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP p...Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.展开更多
BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hem...BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.展开更多
Objective:To explore the impacts of bone marrow mesenchymal stem cells(BMSCs)intervention on the neuronal withering and autophagy in rats after subarachnoid hemorrhage(SAH)in rats and its process.Methods:forty-eight S...Objective:To explore the impacts of bone marrow mesenchymal stem cells(BMSCs)intervention on the neuronal withering and autophagy in rats after subarachnoid hemorrhage(SAH)in rats and its process.Methods:forty-eight SD rats(males),were randomly assigned to the followings:sham surgery(Sham)group,modeling(SAH)group,modeling group+bone marrow mesenchymal stem cells(BMSCs)group,the modeling group+BMSCs+AMPK inhibitor(Compound C)group,twelve rats in each group.Except Sham group,other groups formed SAH samples with intravascular points.Separate groups Compound C and BMSCs,respectively Compound C and 10μL of normal saline were injected into the left lateral ventricle of rats using a stereoscope brain machine 30 minutes before modeling,and 2μL concentration is 1×10^(8)/mL cell suspension was injected into the ventricles of the brain 1 hour after the model was established.Observe whether the rats have severe brain swelling.Garcia were used to test the neural function of rats.TUNEL staining was used to monitor neuronal apoptosis in the rat hippocampal gyrus.Immunohistochemical fluorescence reflected the expression of two proteins,LC3-II and Beclin-1,in rat hippocampal gyrus.Western blotting is applied to measure the expressions of autophagy-associated proteins in the AMPK pathway.Results:Compared with the group undergoing sham-surgery,brain edema worsened in the model group,neuronal apoptosis rate was increased,neural function was weakened,Protein granules decreased(P<0.05)and expression levels of p-AMPK and other proteins decreased(P<0.05);brain swelling and neuronal apoptosis were reduced in the BMSCs group by comparison with the modeling group’s,with substantial elevation in the expression of proteins comprising LC3-Ⅱ,Beclin-1,and p-AMPK.And the standard of p-mTOR protein expression was considerably lessened(P<0.05);rats belonging to group compound C showed increased brain swelling which is relative to that of BMSCs group,increased neuronal apoptosis,decreased neuronal function(P<0.05),increased p-AMPK protein expression,and decreased LC3-Ⅱ,Beclin-1,and p-mTOR protein expression(P<0.05).Conclusion:BMSCs transplantation can reduce neuronal apoptosis after SAH;its principle may be to activate AMPK/mTOR pathway,strengthen autophagy of neurons,and thus inhibit their transformation to apoptosis.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
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
The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid ...The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied.A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool.Some rats were first treated with JAK2/STAT3 small interfering RNA(Si-JAK2/Si-STAT3)or overexpression plasmids of JAK2/STAT3.In the brains of subarachnoid hemorrhage model rats,the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated,reaching a peak at 48 hours after injury.Simultaneously,the interactions between JAK2 and SOCS1 were reduced.In contrast,the interactions between JAK2 and STAT3 were markedly enhanced.Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis,destruction of the blood-brain barrier,brain edema,and cognitive functional impairment after subarachnoid hemorrhage.This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein,decreased total levels of JAK2 and STAT3 protein,and increased SOCS1 protein expression.However,overexpression of JAK2 and STAT3 exerted opposite effects,aggravating subarachnoid hemorrhage-induced early brain injury.Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors(inducible nitric oxide synthase,interleukin-1β,and tumor necrosis factor-α)and increased the release of anti-inflammatory factors(arginase-1,interleukin-10,and interleukin-4).Furthermore,primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro,and the JAK2 inhibitor AG490 was used as an intervention.The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression.Together,our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses.This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China(approval No.LLSC-20180202)on March 1,2018.展开更多
Delayed ischemic neurologic deficit after subarachnoid hemorrhage results from loss of neural cells.Nerve growth factor and its receptor Trk A may promote regeneration of neural cells,but their expression after subara...Delayed ischemic neurologic deficit after subarachnoid hemorrhage results from loss of neural cells.Nerve growth factor and its receptor Trk A may promote regeneration of neural cells,but their expression after subarachnoid hemorrhage remains unclear.In the present study,a rat model of subarachnoid hemorrhage was established using two injections of autologous blood into the cistern magna.Immunohistochemical staining suggested that the expression of nerve growth factor and Trk A in the cerebral cortex and brainstem increased at 6 hours,peaked at 12 hours and decreased 1 day after induction of subarachnoid hemorrhage,whereas the expression in the hippocampus increased at 6 hours,peaked on day 1,and decreased 3 days later.Compared with those for the rats in the sham and saline groups,neurobehavioral scores decreased significantly 12 hours and 3 days after subarachnoid hemorrhage（P 〈 0.05）.These results suggest that the expression of nerve growth factor and its receptor Trk A is dynamically changed in the rat brain and may thus participate in neuronal survival and nerve regeneration after subarachnoid hemorrhage.展开更多
Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologou...Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna.Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage,12 and 36 hours after subarachnoid hemorrhage.Compared with the controls,atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage,neurological function had clearly improved;brain edema was remarkably relieved;cell apoptosis was markedly reduced in the cerebral cortex of rats;the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only.The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated.The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage.However,these were contrary to the results of 3-methyladenine injection,which inhibits the signaling pathway of autophagy.These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy.The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University,China(904 Hospital of Joint Logistic Support Force of PLA;approval No.YXLL-2017-09)on February 22,2017.展开更多
Visual field defect is one of the various clinical manifestations in patients with subarachnoid hemorrhage（SAH）. Little is known about the pathogenic mechanism of visual field defect in SAH. In the current study,we ...Visual field defect is one of the various clinical manifestations in patients with subarachnoid hemorrhage（SAH）. Little is known about the pathogenic mechanism of visual field defect in SAH. In the current study,we investigated the diffusion tensor imaging （DTI） finding of the optic radiation in patients with SAH followingrupture of a cerebral artery aneurysm. We recruited 21 patients with aneurismal SAH （12 males, 9 females, mean age, 52.67 years; range, 41–68 years） who showed no definite lesion along the visual pathway.Twenty-one age-and sex-matched normal control subjects were also recruited. DTI data were acquired at an average of 5.9 weeks （range： 3–12 weeks） after onset and reconstruction of the optic radiation was performed using DTI-Studio software. The fractional anisotropy value, apparent diffusion coefficient value,and fiber number of the optic radiation were measured. The fractional anisotropy value of the optic radiation was significantly decreased, and the apparent diffusion coefficient value was significantly increased, in patients with aneurismal SAH than in normal control subjects. However, there was no significant difference in the fiber number of the optic radiation between patients with aneurismal SAH and normal control subjects. The decrement of fractional anisotropy value and increment of apparent diffusion coefficient value of the optic radiation in patients with aneurismal SAH suggest optic radiation injury. Therefore, we recommend a thorough evaluation for optic radiation injury in patient with aneurismal SAH.展开更多
Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascula...Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.展开更多
Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring ...Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.展开更多
Serum biomarkers may play a reliable role in predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage. This study retrospectively analyzed the relationship between serum biomarkers on admission and ...Serum biomarkers may play a reliable role in predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage. This study retrospectively analyzed the relationship between serum biomarkers on admission and outcomes in patients with aneurysmal subarachnoid hemorrhage. We recruited 146 patients with aneurysmal subarachnoid hemorrhage who were treated in Renmin Hospital of Wuhan University of China between 1 May 2014 and 30 March 2016. There were 57 males and 89 females included and average age of included patients was 57.03 years old. Serum samples were taken immediately on admission（within 48 hours after initial hemorrhage） and the levels of serum biomarkers were detected. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between biomarkers and clinical outcomes. Receiver operating characteristic curves were obtained to investigate the possibility of the biomarkers predicting prognosis. Of the 146 patients, 102 patients achieved good outcomes and 44 patients had poor outcomes. Univariate and multivariate analyses showed that high World Federation of Neurosurgical Societies grade, high serum D-dimer levels, and high neurological complications were significantly associated with poor outcomes. Receiver operating characteristic curves verified that D-dimer levels were associated with poor outcomes. D-dimer levels strongly correlated with neurological complications. In conclusion, we suggest that D-dimer levels are a good independent prognostic factor for poor outcomes in patients with aneurysmal subarachnoid hemorrhage.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82130037(to CH),81971122(to CH),82171323(to WL)the Natural Science Foundation of Jiangsu Province of China,No.BK20201113(to WL)。
文摘The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.
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Japan Society for the Promotion of Science,Grant/Award Number:22K09110。
文摘The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.
文摘BACKGROUND Subarachnoid hemorrhage is a severe neurological condition that requires prompt and appropriate treatment to prevent complications.Aneurysms are the most common cause of spontaneous subarachnoid hemorrhage.Conversely,basilar artery perforator aneurysms(BAPAs)are a rare etiology.There is no consensus on the optimal management of ruptured BAPAs in the acute setting.CASE SUMMARY We present a case series of 3 patients with ruptured BAPAs who were treated at our institution.Two patients had a modified Fisher grade of I,and one had a grade of IV on initial presentation.The aneurysms were detected by computed tomography angiography in two cases and conventional angiography in one case.The 3 patients underwent endovascular treatment with Guglielmi detachable coils.Post-treatment,the patients had good clinical outcomes,and follow-up brain computed tomography scans showed reduced subarachnoid hemorrhage without any new hemorrhage.However,one patient experienced a cerebral infarction 2 months later and eventually succumbed to the condition.The other 2 patients showed progressive recovery,and no aneurysm recurrence was observed at the 2-year follow-up.CONCLUSION Endovascular treatment may be a preferable approach for managing ruptured BAPAs compared with surgical intervention or conservative management.Early detection and prompt treatment is important to achieve favorable patient outcomes.
文摘Objective:To explore the clinical and pathological characteristics of cerebral venous sinus thrombosis(CVST)with subarachnoid hemorrhage(SAH)and intracerebral hemorrhage(ICH),and to investigate the diagnosis,radiographic changes,and prognosis over the course of treatment.Methods:The clinical data and radiographic findings of a young male CVST patient,who presented with initial symptoms of SAH and ICH,were collected and analyzed.The relevant literature was also reviewed.Results:The patient had no specific clinical symptoms except for headache.The brain computed tomography(CT)scan revealed SAH,a high-density shadow in the right posterior fossa and cerebellar hemisphere,and ICH in the left frontal lobe.Magnetic resonance venography(MRV)further revealed bilateral thrombosis in the transverse and sigmoid sinuses.Conclusion:CVST with SAH and ICH is rare and difficult to diagnose.Careful radiological study and clinical analysis are important for the correct and early diagnosis of this condition.Anticoagulation therapy is considered the primary treatment for CVST.
基金supported by the National Natural Science Foundation of China,Nos.81971870,82172173(both to MCL)。
文摘Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.
基金supported by the National Natural Science Foundation of China,Research on Brain Magnetic Resonance Image Segmentation Based on Particle Computation(No.61672386).
文摘Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.
基金financially supported by grants from Key Research and Development Projects of Zhejiang Province (2020C03071)the Construction Fund of Medical Key Disciplines of Hangzhou (OO20200485, OO20200055)。
文摘BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.
基金Tangshan Science,Technology and Development Plan Project (21130224C)Hebei Province 2022 Medical Science Research Project Plan (20221533)College Student Innovation Training Program (R2022166)。
文摘Objective:To explore the impacts of bone marrow mesenchymal stem cells(BMSCs)intervention on the neuronal withering and autophagy in rats after subarachnoid hemorrhage(SAH)in rats and its process.Methods:forty-eight SD rats(males),were randomly assigned to the followings:sham surgery(Sham)group,modeling(SAH)group,modeling group+bone marrow mesenchymal stem cells(BMSCs)group,the modeling group+BMSCs+AMPK inhibitor(Compound C)group,twelve rats in each group.Except Sham group,other groups formed SAH samples with intravascular points.Separate groups Compound C and BMSCs,respectively Compound C and 10μL of normal saline were injected into the left lateral ventricle of rats using a stereoscope brain machine 30 minutes before modeling,and 2μL concentration is 1×10^(8)/mL cell suspension was injected into the ventricles of the brain 1 hour after the model was established.Observe whether the rats have severe brain swelling.Garcia were used to test the neural function of rats.TUNEL staining was used to monitor neuronal apoptosis in the rat hippocampal gyrus.Immunohistochemical fluorescence reflected the expression of two proteins,LC3-II and Beclin-1,in rat hippocampal gyrus.Western blotting is applied to measure the expressions of autophagy-associated proteins in the AMPK pathway.Results:Compared with the group undergoing sham-surgery,brain edema worsened in the model group,neuronal apoptosis rate was increased,neural function was weakened,Protein granules decreased(P<0.05)and expression levels of p-AMPK and other proteins decreased(P<0.05);brain swelling and neuronal apoptosis were reduced in the BMSCs group by comparison with the modeling group’s,with substantial elevation in the expression of proteins comprising LC3-Ⅱ,Beclin-1,and p-AMPK.And the standard of p-mTOR protein expression was considerably lessened(P<0.05);rats belonging to group compound C showed increased brain swelling which is relative to that of BMSCs group,increased neuronal apoptosis,decreased neuronal function(P<0.05),increased p-AMPK protein expression,and decreased LC3-Ⅱ,Beclin-1,and p-mTOR protein expression(P<0.05).Conclusion:BMSCs transplantation can reduce neuronal apoptosis after SAH;its principle may be to activate AMPK/mTOR pathway,strengthen autophagy of neurons,and thus inhibit their transformation to apoptosis.
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.
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This study was supported by the National Natural Science Foundation of China,No.81500375(to XQK)the Fundamental Research Funds for the Central Universities,No.WK9110000112(to YW)+1 种基金the Anhui Provincial Natural Science Foundation of China,No.1508085QH184(to YW)Shandong Provincial Natural Science Foundation of China,No.ZR2015HQ001(to XQK).
文摘The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied.A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool.Some rats were first treated with JAK2/STAT3 small interfering RNA(Si-JAK2/Si-STAT3)or overexpression plasmids of JAK2/STAT3.In the brains of subarachnoid hemorrhage model rats,the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated,reaching a peak at 48 hours after injury.Simultaneously,the interactions between JAK2 and SOCS1 were reduced.In contrast,the interactions between JAK2 and STAT3 were markedly enhanced.Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis,destruction of the blood-brain barrier,brain edema,and cognitive functional impairment after subarachnoid hemorrhage.This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein,decreased total levels of JAK2 and STAT3 protein,and increased SOCS1 protein expression.However,overexpression of JAK2 and STAT3 exerted opposite effects,aggravating subarachnoid hemorrhage-induced early brain injury.Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors(inducible nitric oxide synthase,interleukin-1β,and tumor necrosis factor-α)and increased the release of anti-inflammatory factors(arginase-1,interleukin-10,and interleukin-4).Furthermore,primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro,and the JAK2 inhibitor AG490 was used as an intervention.The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression.Together,our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses.This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China(approval No.LLSC-20180202)on March 1,2018.
基金funded by the National Natural Science Foundation of China,No.30870844the New Century Supporting Program to Excellent Talents in China,No.NCET-05-0831
文摘Delayed ischemic neurologic deficit after subarachnoid hemorrhage results from loss of neural cells.Nerve growth factor and its receptor Trk A may promote regeneration of neural cells,but their expression after subarachnoid hemorrhage remains unclear.In the present study,a rat model of subarachnoid hemorrhage was established using two injections of autologous blood into the cistern magna.Immunohistochemical staining suggested that the expression of nerve growth factor and Trk A in the cerebral cortex and brainstem increased at 6 hours,peaked at 12 hours and decreased 1 day after induction of subarachnoid hemorrhage,whereas the expression in the hippocampus increased at 6 hours,peaked on day 1,and decreased 3 days later.Compared with those for the rats in the sham and saline groups,neurobehavioral scores decreased significantly 12 hours and 3 days after subarachnoid hemorrhage（P 〈 0.05）.These results suggest that the expression of nerve growth factor and its receptor Trk A is dynamically changed in the rat brain and may thus participate in neuronal survival and nerve regeneration after subarachnoid hemorrhage.
基金supported by the Wuxi Foundation for Development of Science and Technology of China,No.WX18IIAN041(to JHC)the Major Project of Nanjing Military Area Research Fund of China,No.15DX003(to JHC)the Wuxi Youth Medical Fund of China,No.QNRC046(to TW)
文摘Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna.Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage,12 and 36 hours after subarachnoid hemorrhage.Compared with the controls,atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage,neurological function had clearly improved;brain edema was remarkably relieved;cell apoptosis was markedly reduced in the cerebral cortex of rats;the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only.The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated.The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage.However,these were contrary to the results of 3-methyladenine injection,which inhibits the signaling pathway of autophagy.These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy.The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University,China(904 Hospital of Joint Logistic Support Force of PLA;approval No.YXLL-2017-09)on February 22,2017.
基金supported by the National Research Foundation(NRF)of Korea Grant funded by the Korean Government(MSIP)(2015R1A2A2A01004073)
文摘Visual field defect is one of the various clinical manifestations in patients with subarachnoid hemorrhage（SAH）. Little is known about the pathogenic mechanism of visual field defect in SAH. In the current study,we investigated the diffusion tensor imaging （DTI） finding of the optic radiation in patients with SAH followingrupture of a cerebral artery aneurysm. We recruited 21 patients with aneurismal SAH （12 males, 9 females, mean age, 52.67 years; range, 41–68 years） who showed no definite lesion along the visual pathway.Twenty-one age-and sex-matched normal control subjects were also recruited. DTI data were acquired at an average of 5.9 weeks （range： 3–12 weeks） after onset and reconstruction of the optic radiation was performed using DTI-Studio software. The fractional anisotropy value, apparent diffusion coefficient value,and fiber number of the optic radiation were measured. The fractional anisotropy value of the optic radiation was significantly decreased, and the apparent diffusion coefficient value was significantly increased, in patients with aneurismal SAH than in normal control subjects. However, there was no significant difference in the fiber number of the optic radiation between patients with aneurismal SAH and normal control subjects. The decrement of fractional anisotropy value and increment of apparent diffusion coefficient value of the optic radiation in patients with aneurismal SAH suggest optic radiation injury. Therefore, we recommend a thorough evaluation for optic radiation injury in patient with aneurismal SAH.
基金the Natural Science Foundation of Jiangsu Province(Youth Program),No.BK20190129National Scientific Program of Jiangsu Colleges and Universities of China,No.19KJB320012(both to LY)。
文摘Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.
文摘Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.
文摘Serum biomarkers may play a reliable role in predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage. This study retrospectively analyzed the relationship between serum biomarkers on admission and outcomes in patients with aneurysmal subarachnoid hemorrhage. We recruited 146 patients with aneurysmal subarachnoid hemorrhage who were treated in Renmin Hospital of Wuhan University of China between 1 May 2014 and 30 March 2016. There were 57 males and 89 females included and average age of included patients was 57.03 years old. Serum samples were taken immediately on admission（within 48 hours after initial hemorrhage） and the levels of serum biomarkers were detected. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between biomarkers and clinical outcomes. Receiver operating characteristic curves were obtained to investigate the possibility of the biomarkers predicting prognosis. Of the 146 patients, 102 patients achieved good outcomes and 44 patients had poor outcomes. Univariate and multivariate analyses showed that high World Federation of Neurosurgical Societies grade, high serum D-dimer levels, and high neurological complications were significantly associated with poor outcomes. Receiver operating characteristic curves verified that D-dimer levels were associated with poor outcomes. D-dimer levels strongly correlated with neurological complications. In conclusion, we suggest that D-dimer levels are a good independent prognostic factor for poor outcomes in patients with aneurysmal subarachnoid hemorrhage.
