Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.

Background: Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators. Methods: We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out sensitivity analyses was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results. Results: Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552]. Conclusion: Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

Sequencing of neurofilament genes identified NEFH Ser787Arg as a novel risk variant of sporadic amyotrophic lateral sclerosis in Chinese subjects.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with neuronal cell inclusions composed of neurofilaments and other abnormal aggregative proteins as pathological hallmarks. Approximately 90% of patients have sporadic cases (sALS), and at least 4 genes, i.e. C9orf72, SOD1, FUS and TARDBP, have been identified as the main causative genes, while many others have been proposed as potential risk genes. However, these mutations could explain only ~ 10% of sALS cases. The neurofilament polypeptides encoded by NEFH, NEFM, and NEFL are promising protein biomarkers for ALS and other degenerative diseases. However, whether the genetic variants of these genes were associated with ALS remain ambiguous. METHODS: Here, we used PCR-Sanger to sequence the exons of these three genes in a cohort of 371 sALS patients and 711 healthy controls (Phase I) and validated the risk variant in another 300 sALS patients and 1076 controls (Phase II). RESULTS: A total of 92 variants were identified, including 36 rare heterozygous variants in NEFH, 27 in NEFM, and 16 in NEFL, and only rs568759161 (p.Ser787Arg) in NEFH reached nominal statistical power (P = 0.02 at Phase I, P = 0.009 at Phase II) in the case-control comparison. Together, the Phase I and II studies showed the significantly higher frequency of the variant in cases (9/1342, 0.67%) than in controls (2/3574, 0.07%) (OR 12.06; 95% CI 2.60-55.88; P = 0.0003). No variants passed multiple testing in the discovery cohort, but rs568759161 was associated with ALS in a replication cohort. CONCLUSIONS: Our results confirmed that NEFH Ser787Arg is a novel sALS risk variant in Chinese subjects, but NEFM and NEFL were not associated with sALS. These data may have implications for genetic counselling and for understanding the pathogenesis of sALS.

Novel FUS mutation Y526F causing rapidly progressive familial amyotrophic lateral sclerosis.

FUS gene is one of the most common mutated genes in amyotrophic lateral sclerosis (ALS). We sequenced for FUS mutations in a cohort of 15 familial ALS and 275 sporadic ALS of Chinese origin. All 15 exons of the FUS gene were sequenced by targeted next-generation sequencing in a cohort of 15 familial ALS indexes and 275 sporadic ALS patients of Chinese origin. One novel p.Y526F mutation in FUS was detected in one familial ALS proband. Another novel FUS p.Q140R variant and two known FUS mutations (p.R495Efs*33 and p.R521C) were identified in four sporadic ALS cases. The frequency of FUS mutation in our cohort is 6.7% in familial ALS and 1.5% in sporadic ALS. The familial ALS proband carrying the FUS p.Y526F mutation presented with juvenile-onset lower limbs weakness and demonstrated an aggressive course, with respiratory muscles involvement 6 months after onset. The other patients in the family all had limbs weakness and died 1-2 years after disease onset. Our results strengthen that FUS mutations are the most frequent genetic causes of young-onset aggressive ALS. Genetic testing of the FUS gene should be performed in early-onset ALS patients especially those with a rapid progression.

Over-expression of 5-HT6 Receptor and Activated Jab-1/p-c-Jun Play Important Roles in Pilocarpine-Induced Seizures and Learning-Memory Impairment.

Cognitive impairment is a common comorbidity in patients with temporal lobe epilepsy (TLE) that severely affects patients' quality of life. Also, serotonin 5-hydroxytryptamine 6 (5-HT6) receptor plays an important role in cognition. This study aimed to investigate effects of 5-HT6 receptor on learning-memory capacities in epileptic rats. Total of 36 adult Sprague-Dawley (SD) rats were divided into vehicle (n = 6) and epileptic group (n = 30). Status epilepticus (SE) was induced via systemic injection of pilocarpine. Epileptic group was sub-divided into vehicle, 10, 20, and 30 µg SB-271046 groups, six mice per group. Learning-memory performance of rats was evaluated by using Y maze and Morris water maze test. 5-HT6 receptor expression was examined using immunostaining and Western blot. The other six rats were used to make epileptic model and Jab-1/p-c-Jun were detected. Results showed that frequency of spontaneous recurrent seizures (SRSs) was significantly decreased in pilocarpine-induced epileptic rats that treated with SB-271046. Alternation rate and new arm percentage were decreased in epileptic rats compared to control. The 5-day mean latency was prolonged in epileptic rats compared to control rats. During retention stage, mean latency, number of target crossings, and percentage of time spent in target zone were decreased in epileptic rats, but not in those treated with SB-271046. The number of apoptotic neurons was significantly increased in epileptic rats, which was decreased by SB-271046. 5-HT6 expression was significantly increased in hippocampus and cortex following recurrent seizures. Jab-1 level was decreased after SB-271046 administration. p-c-Jun level was elevated in epileptic rats and decreased in a dose-dependent manner after the SB-271046 administration. In conclusion, the over-expression of 5-HT6 receptor and activated Jab-1/p-c-Jun plays an important role in pilocarpine-induced seizures and learning-memory impairment.

Novel insights into the effect of paroxetine administration in pilocarpine­induced chronic epileptic rats.

The aim of the present study was to investigate the role of paroxetine intervention in epilepsy, and its association with the expression of serotonin transporter (SERT) and hippocampal apoptosis. Thirty adult male Sprague Dawley rats were divided into control vehicle (n=6) and epileptic (n=24) groups. Status epilepticus (SE) was induced via systemic injection of pilocarpine, and seizure activity was monitored via video electroencephalogram. The epileptic group was then randomly divided into two groups; Four weeks following SE induction, paroxetine (5 mg/kg/day; SE + paroxetine group) or normal saline (SE group) was intraperitoneally injected for 4 weeks. Brain tissue was collected to evaluate apoptosis via terminal deoxynucleotidyl transferase dUTP nick­end labeling. SERT, B­cell lymphoma­2 (Bcl­2) and brain derived neurotropic factor (BDNF) expression levels were evaluated by western blotting, and miR­16 expression was evaluated by reverse transcription­quantitative polymerase chain reaction. Paroxetine did not affect the mortality of the pilocarpine­induced chronic epileptic rats. Spontaneous recurrent seizures (SSRs) were observed 7­28 days following SE induction. The frequency and stage of the SSRs were reduced by paroxetine administration. Apoptotic cells were observed in the epileptic hippocampus. Following paroxetine intervention, the staining intensity and number of apoptotic cells were significantly decreased. Expression levels of BDNF and Bcl­2 were lower in the SE group compared with the vehicle group. The former was not altered by paroxetine injection; however, the latter was increased. In the SE group, SERT expression was not altered in the raphe nucleus but was decreased in the hippocampus. Following paroxetine administration, SERT expression was decreased in the raphe nucleus and increased in the hippocampus. In the SE group, miR­16 expression was decreased in the raphe nucleus and increased in the hippocampus. Following paroxetine administration, miR­16 expression was not altered in the raphe nucleus but was reduced in the hippocampus. In conclusion, the seizures and hippocampal apoptosis observed in chronic epileptic rats were alleviated by paroxetine treatment. This effect may be associated with the reduced Bcl­2 and BDNF expression and the modulation of SERT expression. The alterations in miR­16 expression may provide a potential explanation for the modulation of apoptosis; however, further research is required to determine the complete underlying molecular mechanism.

The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats.

OBJECTIVE: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. METHODS: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm's staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. RESULTS: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. CONCLUSION: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.

Surgical treatment of pituitary apoplexy in association with hemispheric infarction.

We report a patient with pituitary apoplexy in whom cerebral infarction developed, possibly secondary to vasospasm. Pituitary apoplexy is a clinical syndrome caused by acute hemorrhage or infarction of the pituitary gland. Our patient's clinical symptoms and radiographic findings greatly improved after surgical resection of the apoplectic pituitary gland. An extensive literature review was performed, including all previously reported cases of pituitary apoplexy leading to cerebral infarction. The clinical features, pathophysiological mechanisms, management and outcome of cerebral infarction following pituitary apoplexy are discussed. We show that cerebral infarction following pituitary apoplexy is associated with much poor prognosis. Early surgical decompression of the tumor and hemisphere should be performed in patients with severe or progressive neurological deficits, however, those with less severe presentations may be treated conservatively or with delayed elective surgery.

Mild clinical manifestation and unusual recovery upon coenzyme Q10 treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one­year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

[The effects of adipose-derived stem cells transplantation on the expression of TGF-ß1 in rat brain after cerebral ischemia].

AIM: To explore the mechanisms of adipose-derived stem cells (ADSCs) transplanting induced angiogenesis in rat brain after focal cerebral ischemia. METHODS: 108 male adult Sprague-Dawley rats were randomly assigned into 4 groups: sham-operated group, middle cerebral artery occlusion (MCAO) group, vehicle group and MCAO+ADSCs-treated group. Rat's focal cerebral ischemia model was established by right middle cerebral artery occlusion (MCAO) with modified Longa's method. ADSCs were pre-labeled by CFSE before the transplantation into the rat brain. At 1 d after MCAO, 30 µL cell suspension which contained 1×10(6); ADSCs was injected into the lateral ventricle of MCAO+ADSCs-treated rats, and the same dose of PBS was given to the rats of vehicle group as control. At 4 d, 7 d and 14 d after MCAO, rats were decapitated to detect the TGF-ß1 expression in the infarct area. RESULTS: The expression of TGF-ß1 in brain tissues in MCAO+ADSCs-treated group was significantly higher than MCAO group and vehicle group at 4 d, 7 d and 14 d after MCAO, respectively. After transplantation into MCAO rats, ADSCs could survive and express TGF-ß1 in the ischemic brain. CONCLUSION: These data suggest that ADSCs transplantation can promote revascularization in cerebral ischemic rats, partly by promoting TGF-ß1 expression in the brain.

Microglial phagocytosis induced by fibrillar ß-amyloid is attenuated by oligomeric ß-amyloid: implications for Alzheimer's disease.

BACKGROUND: Reactive microglia are associated with ß-amyloid (Aß) deposit and clearance in Alzhiemer's Disease (AD). Paradoxically, entocranial resident microglia fail to trigger an effective phagocytic response to clear Aß deposits although they mainly exist in an "activated" state. Oligomeric Aß (oAß), a recent target in the pathogenesis of AD, can induce more potent neurotoxicity when compared with fibrillar Aß (fAß). However, the role of the different Aß forms in microglial phagocytosis, induction of inflammation and oxidation, and subsequent regulation of phagocytic receptor system, remain unclear. RESULTS: We demonstrated that Aß(1-42) fibrils, not Aß(1-42) oligomers, increased the microglial phagocytosis. Intriguingly, the pretreatment of microglia with oAß(1-42) not only attenuated fAß(1-42)-triggered classical phagocytic response to fluorescent microspheres but also significantly inhibited phagocytosis of fluorescent labeled fAß(1-42). Compared with the fAß(1-42) treatment, the oAß(1-42) treatment resulted in a rapid and transient increase in interleukin 1ß (IL-1ß) level and produced higher levels of tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2) and intracellular superoxide anion (SOA). The further results demonstrated that microglial phagocytosis was negatively correlated with inflammatory mediators in this process and that the capacity of phagocytosis in fAß(1-42)-induced microglia was decreased by IL-1ß, lippolysaccharide (LPS) and tert-butyl hydroperoxide (t-BHP). The decreased phagocytosis could be relieved by pyrrolidone dithiocarbamate (PDTC), a nuclear factor-κB (NF-κB) inhibitor, and N-acetyl-L-cysteine (NAC), a free radical scavenger. These results suggest that the oAß-impaired phagocytosis is mediated through inflammation and oxidative stress-mediated mechanism in microglial cells. Furthermore, oAß(1-42) stimulation reduced the mRNA expression of CD36, integrin ß1 (Itgb1), and Ig receptor FcγRIII, and significantly increased that of formyl peptide receptor 2 (FPR2) and scavenger receptor class B1 (SRB1), compared with the basal level. Interestingly, the pre-stimulation with oAß(1-42) or the inflammatory and oxidative milieu (IL-1ß, LPS or t-BHP) significantly downregulated the fAß(1-42)-induced mRNA over-expression of CD36, CD47 and Itgb1 receptors in microglial cells. CONCLUSION: These results imply that Aß oligomers induce a potent inflammatory response and subsequently disturb microglial phagocytosis and clearance of Aß fibrils, thereby contributing to an initial neurodegenerative characteristic of AD. Antiinflammatory and antioxidative therapies may indeed prove beneficial to delay the progression of AD.

A neurofibromatosis type 1 patient with thoracic encapsulated fluid and intracranial hypotension syndrome: a case report.

INTRODUCTION: Spinal meningoceles are uncommon entities, mostly associated with neurofibromatosis type 1 (NF-1). Their intrusion into the thoracic cavity, which compresses lung tissue, is quite often mistaken as a "pleural effusion." The withdrawal of a large amount of "pleural effusion" can lead to the intracranial hypotension syndrome (IHS), herniation, or even death. CASE REPORT: A 43-year-old woman, with NF-1 and a large "pleural effusion" which compressed lung tissue, was admitted to the Thoracic Department due to the patient's shortness of breath during her physical activities. The patient complained of headache shortly after withdrawal of about 250 mL of "pleural effusion." She was diagnosed with IHS according to the typical symptoms of postural headache, low cerebrospinal fluid (CSF) pressure and magnetic resonance imaging findings of diffuse pachymeningeal gadolinium enhancement. The "pleural effusion" was examined and found to be CSF. CONCLUSION: The reported case is the first 1 in the literature in which the intrusion of the NF-1 patient's spinal meningoceles into the thoracic cavity was diagnosed as a "pleural effusion" and large CSF withdrawal led to IHS. We highlight the possibility that thoracic meningoceles can coexist with a thoracic spinal deformity and the caution that needs to be taken when cases with similar symptoms are subjected to withdrawal of fluid.

Tripchlorolide protects neuronal cells from microglia-mediated beta-amyloid neurotoxicity through inhibiting NF-kappaB and JNK signaling.

Recent research has focused on soluble oligomeric assemblies of beta-amyloid peptides (Abeta) as the proximate cause of neuroinflammation, synaptic loss, and the eventual dementia associated with Alzheimer's disease (AD). In this study, tripchlorolide (T4), an extract of Tripterygium wilfordii Hook. F (TWHF), was studied as a novel agent to suppress neuroinflammatory process in microglial cells and to protect neuronal cells against microglia-mediated oligomeric Abeta toxicity. T4 significantly attenuated oligomeric Abeta(1-42)-induced release of inflammatory productions such as tumor necrosis factor-alpha, interleukin-1beta, nitric oxide (NO), and prostaglandin E2. It also downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglial cells. Further molecular mechanism study demonstrated that T4 inhibited the nuclear translocation of nuclear factor-kappaB (NF-kappaB) without affecting I-kappaBalpha phosphorylation. It repressed Abeta-induced JNK phosphorylation but not ERK or p38 MAPK. The inhibition of NF-kappaB and JNK by T4 is correlated with the suppression of inflammatory mediators in Abeta-stimulated microglial cells. These results suggest that T4 protects neuronal cells by blocking inflammatory responses of microglial cells to oligomeric Abeta(1-42) and that T4 acts on the signaling of NF-kappaB and JNK, which are involved in the modulation of inflammatory response. Therefore, T4 may be an effective agent in modulating neuroinflammatory process in AD.

Neuroprotective role of tripchlorolide on inflammatory neurotoxicity induced by lipopolysaccharide-activated microglia.

A large body of evidence has suggested a strong association between neuroinflammation and the pathogenesis of many neurodegenerative diseases. Therefore, it is a good target for therapeutic treatment. So far, studies have proven anti-inflammatory herbal medicine and its constituents to be effective in slowing down the neurodegenerative process. The present study tested tripchlorolide, an extract of Tripterygium wilfordii Hook F (TWHF), as a novel agent to suppress inflammatory process in microglia. It showed this novel agent to be cytotoxic at a dose of 20-40 nM to primary microglia and BV-2 microglial cells but not to primary cortical neurons and Neuro-2A cells in vitro. Moreover, tripchlorolide protected primary cortical neurons and Neuro-2A cells from neuroinflammatory toxicity induced by the conditioned media from lipopolysaccharide (LPS)-stimulated microglia, which resulted in a significant decrease in their cell survival. The changes of the inflammatory mediators in this process were further investigated. In the LPS-stimulated microglia, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular superoxide anion (SOA) was markedly attenuated by tripchlorolide at a dose of 1.25-10 nM in a dose-dependent manner. Furthermore, the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was also significantly inhibited by tripchlorolide in both mRNA and protein levels. These results suggest that tripchlorolide can protect neuronal cells via a mechanism involving inhibition of inflammatory responses of microglia to pathological stimulations. Therefore, it is potentially a highly effective therapeutic agent in treating neuroninflammatory diseases.

[Effects of bone marrow-derived mesenchymal stem cells transplantation on recovery of neurological functions and expression of synaptophysin in focal cerebral infarction in rats].

AIM: To investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) transplantation on the recovery of neurological functions and the expression of synaptophysin in focal cerebral infarction in rats. METHODS: 72 male adult Sprague-Dawley rats were randomly divided into 4 groups (18 in each group): shamoperated group, middle cerebral artery occlusion (MCAO) roup,vehicle group and MCAO+BMSC-treated group. A permanent focal cerebral ischemia model was established using modified Longa's method. BMSC was labeled by DAPI before the transplantation. One day after right middle cerebral artery occlusion(MCAO), 1 x 10(6) cells were injected into the lateral ventricle of rats in BMSCs-treated group and the same dose of PBS was given to the rats in vehicle group. Before sacrificed and at 4 d, 7 d and 14 d after MCAO, the neurological functions were tested by balance beam, rota-rod and screen prehensile and the synaptophysin was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical method. RESULTS: DAPI stained positive cells were observed around the cerebral infarcted area in the BMSC-treated group. Compared with the MCAO group and the vehicle group,the neurological functions in BMSC-treated group were better on 7 d and 14 d after MCAO (P<0.05 or P<0.01), and the synaptophysin around the cerebral infarcted area was significantly upregulated on 4 d, 7 d and 14 d after MCAO (all P<0.01). CONCLUSION: BMSC transplantation can improve the neurological functions by upregulating the expression of synaptophysin after MCAO in rats.

[The effect of interleukin-10 on neurocyte apoptosis in cerebral ischemia in rats].

AIM: To investigate the effect of interleukin-10 on neurocyte apoptosis in cerebral ischemia in rats. METHODS: 36 adult male Sprague-Dawley rats were randomly assigned into 3 groups: sham operation group, middle cerebral artery occlusion(MCAO) group and MCAO+interleukin-10 treatment group. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining was used to detect in situ cell apoptosis, immunohistochemical staining and RT-PCR were used to detect the expression of proapoptotic gene Fas, Fas ligand (FasL) and caspase-3 in peri-infarct, respectively. RESULTS: Cerebral ischemia significantly induced neurocyte apoptosis and upregulated the expression of Fas, FasL and caspase-3, repcetively (P<0.05). IL-10 treatment significantly inhibited neurocyte apoptosis, and suppressed the expression of proapoptotic gene FasL and caspase-3, repcetively (P<0.05), but had no obvious effect on Fas expression (P>0.05). CONCLUSION: IL-10 can suppress neurocyte apoptosis in cerebral ischemia, whose mechanisms seemed related to inhibiting the expression of proapoptotic gene FasL and caspase-3.