Postoperative hydrocephalus is a common complication following posterior fossa tumor resection, affecting 7–40

PURPOSE:The aim of this study was to analyze the correlation between pituitary function and obstructive sleep apnea (OSA) in pituitary adenomas (PA) patients, and to investigate the effect of related hormone levels on the severity of OSA. METHODS:The clinical data of 82 patients with PA aged 18-70 years admitted to the Department of Neurosurgery, Xi'an Jiaotong University Affiliated Hospital from March 2023 to February 2025 were retrospectively collected and divided into functional and non-functional PA group. RESULTS:Functional PA patients were younger and had a higher platelet-lymphocyte ratio (all p < 0.05). Among the PSG related parameters, Patients with functional PA showed higher apnea-hypopnea index (AHI), total sleep time spent with arterial oxygen saturation<90 % and longest apnea duration and oxygen desaturation index with >3 % desaturation (all p < 0.01). In terms of pituitary function parameters, free triiodothyronine (FT3) and insulin-like growth factor-1 (IGF-1) were significantly increased in OSA group, while the levels of cortisol, estradiol and progesterone were all lower (all p < 0.05). Correlation analysis showed that AHI was positively correlated with FT3 and IGF-1. After adjusting for confounding factors, mediation analysis based on regression revealed that FT3 and IGF-1 mediated the association between PA and OSA severity. CONCLUSION:OSA was more severe in functional PA patients compared with non-functional PA patients. FT3 and IGF-1 are reliable predictors of AHI in PA patients, and may become important indicators for early clinical diagnosis of OSA in PA patients. Larger prospective studies are needed to further clarify the relationship between PA and OSA in the future.

OBJECTIVE:To clarify the effects and mechanism of interleukin-17A (IL-17) in hyperglycemia (HG)-induced blood-brain barrier (BBB) breakdown following diffuse axonal injury (DAI). METHODS:Differentially expressed proteins (DEPs) were identified by proteomic analysis via 4D-SmartDIA between control and high-glucose groups of BBB model established by bEnd.3 cells in vitro. A rat model of DAI was built using an instantaneous rotational damage device, and HG was mimicked by intraperitoneal (i.p.) injection of 50% glucose. The localization and expression of the IL-17 receptor (IL-17R) were tested by double-label immunofluorescence and western blotting. IL-17 levels in brain tissue and serum, as well as the concentrations of inflammatory factors, were examined. Axonal injury morphology was evaluated via transmission electron microscopy (TEM) and immunohistochemical detection of β-amyloid precursor protein (β-APP) and neurofilament light chain and heavy chain (NF-L, NF-H). Glial response and apoptosis were also assessed. The detection of BBB permeability was via levels of Evans blue (EB) leakage and tight junction protein. The IL-17 pathway was inhibited using suberoylanilide hydroxamic acid (SAHA), and western blotting was used to detect the phosphorylation (p-p65/t-p65 ratio) of the nuclear factor-κB (NF-κB) pathway. Oxidative stress levels were assessed via colorimetric assays. RESULTS:Proteomic analysis revealed 444 upregulated and 159 downregulated proteins in high-glucose-stimulated bEnd.3 cells compared with those in normal cells, with the IL-17 signaling being one of the most significantly enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. IL-17 and IL-17R expression was elevated in brain tissue and serum following DAI, and HG further enhanced this upregulation; IL-17R was predominantly localized to vascular endothelial cells. HG aggravated axonal injury, increased cortical apoptosis and glial response, promoted BBB disruption, elevated proinflammatory factor levels, and increased oxidative stress after DAI. The inhibition of IL-17 reversed all the damage and protected BBB integrity by maintaining tight junctions and reducing the levels of proinflammatory factors and oxidative stress in vivo. Mechanistically, HG increased NF-κB p65 phosphorylation after DAI, whereas SAHA treatment significantly suppressed this phosphorylation. CONCLUSION:IL-17 mediates HG-induced axonal injury following DAI by destroying BBB integrity via NF-κB-dependent inflammation and oxidative stress, signifying IL-17 as a target for mitigating neurovascular damage in hyperglycemic DAI.

Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone (SVZ) throughout life, responding to various pathophysiological stimuli and playing a crucial role in central nervous system repair. Although numerous studies have elucidated the role of stanniocalcin 2 (STC2) in regulating cell differentiation processes, its specific function in NSPCs differentiation remains poorly understood. Clarifying the role of STC2 in NSPCs is essential for devising novel strategies to enhance the intrinsic potential for brain regeneration postinjury. Our study revealed the expression of STC2 in NSPCs derived from the SVZ of the C57BL/6N mouse. In cultured SVZ-derived NSPCs, STC2 treatment significantly increased the number of Tuj1 and DCX-positive cells. Furthermore, STC2 injection into the lateral ventricle promoted the neuronal differentiation of NSPCs and migration to the olfactory bulb. Conversely, the STC2 knockdown produced the opposite effect. Further investigation showed that STC2 treatment enhanced AKT phosphorylation in cultured NSPCs, whereas STC2 inhibition hindered AKT activation. Notably, the neuronal differentiation induced by STC2 was blocked by the AKT inhibitor GSK690693, whereas the AKT activator SC79 reversed the impact of STC2 knockdown on neuronal differentiation. Our findings indicate that enhancing STC2 expression in SVZ-derived NSPCs facilitates neuronal differentiation, with AKT regulation potentially serving as a key intracellular target of STC2 signaling.

Neural stem/progenitor cells (NSPCs) hold immense promise in clinical applications, yet the harsh conditions resulting from central nervous system (CNS) injuries, particularly oxidative stress, lead to the demise of both native and transplanted NSPCs. Cellular communication network factor 3 (CCN3) exhibits a protective effect against oxidative stress in various cell types. This study investigates the impact of CCN3 on NSPCs apoptosis induced by oxidative stress. To establish models of primary cultured mouse NSPCs under oxidative stress, we exposed them to 50 mu M H2O2 for 4 h. Remarkably, pre -exposing CCN3 exacerbated the H2O2-induced decline in cell viability in a concentration -dependent manner. However, employing gene -targeted siRNA to inhibit CCN3 protected NSPCs against H2O2-induced cell death. Conversely, CCN3 replenishment reversed this protective effect, as evidenced by TUNEL staining, the ratio of Cleaved-caspase-3 to Pro-caspase-3, and Bcl-2/Bax. Further investigations revealed that CCN3 pretreatment increased the phosphorylation level of p38 MAPK, while silencing CCN3 diminished p38 MAPK activation. Ultimately, the impact of changes in CCN3 protein expression on H2O2-induced apoptosis was nullified using anisomycin (a p38 activator) and SB 203580 (a p38 inhibitor). Our findings suggest that CCN3 inhibition prevents H2O2-induced cell death in cultured mouse NSPCs via the p38 pathway. These discoveries may contribute to the development of strategies aimed at enhancing the survival of both endogenous and transplanted NSPCs following CNS oxidative stress insults.

Background and Objectives:Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM.Methods and Results:Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP.Conclusions:Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

Abstract Objectives We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced‐disruption of blood‐brain barrier (BBB) integrity after diffuse axonal injury (DAI). Methods Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium‐binding adapter molecule‐1, β‐amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick‐end labeling (TUNEL) assay. The permeability of blood‐brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) and the nuclear transcription factor kappa B (NF‐κB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol‐12‐myristate‐13‐acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme‐linked immunosorbent assay. Results Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF‐κB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF‐κB pathway abrogated the protective effects of TPPU on BBB integrity in vitro. Conclusions sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF‐κB pathway.

目的 探讨微信辅助下以病例为基础的教学法(CBL教学法)在神经外科住院医师规范化培训垂体腺瘤教学中的作用.方法 选取2019年1月-2021年9月在我院神经外科轮转,进行住院医师规范化培训的学员61名,按轮转批次将学员分为对照组和研究组,在垂体腺瘤的教学中对照组采用传统教学法,研究组采用微信辅助下CBL教学法.在教学培训结束后,对比两组住培学员在垂体腺瘤专病考核中的基础理论成绩、临床思维与分析能力以及临床技能评分,并行教学满意度调查.结果 与对照组相比较,研究组学员在临床思维与分析能力和临床技能方面的评分均显著高于对照组(85.27±5.43 vs 77.36±6.19及80.53±5.99vs 72.42±6.29,P＜0.05);而两组学员的基础理论知识评分相比较则 未见显著性差异(79.89±6.18 vs 80.98±6.52,P＞0.05).在总的教学效果比较中,研究组学员评分显著高于对照组(245.69±16.76vs230.76±18.46,P＜0.05),同时研究组学员的教学满意度亦显著高于对照组(78.13％vs 62.07％,P＜0.05).结论 在神经外科住院医师规范化培训的垂体腺瘤教学中,微信辅助CBL教学法能较好地提高住培学员的临床思维与分析能力、临床技能以及总的教学效果,并获得较好的教学满意度,虽然该方法在一定程度上增加了带教教师和住培学员的负担,但仍值得借鉴和推荐.

— Hyperglycemia aggravates brain damage after diffuse axonal injury (DAI), but the underlying mechanisms are not fully defined. In this study, we aimed to investigate a possible role for hyperglycemia in the disruption of blood–brain barrier (BBB) integrity in a rat model of DAI and the underlying mechanisms. Accordingly, 50% glucose was intraperitoneally injected after DAI to establish the hyperglycemia model. Hyperglycemia treatment aggravated neurological impairment and axonal injury, increased cell apoptosis and glial activation, and promoted the release of inflammatory factors, including TNF-α, IL-1β, and IL-6. It also exacerbated BBB disruption and decreased the expression of tight junction-associated proteins, including ZO-1, claudin-5, and occludin-1, whereas the PPARγ agonist rosiglitazone (RSG) had the opposite effects. An in vitro BBB model was established by a monolayer of human microvascular endothelial cells (HBMECs). Hyperglycemia induction worsened the loss of BBB integrity induced by oxygen and glucose deprivation (OGD) by increasing the release of inflammatory factors and decreasing the expression of tight junction-associated proteins. Hyperglycemia further reduced the expression of PPARγ and caveolin-1, which significantly decreased after DAI and OGD. Hyperglycemia also further increased the expression of toll-like receptor 4 (TLR4), which significantly increased after OGD. Subsequently, the PPARγ agonist RSG increased caveolin-1 expression and decreased TLR4 expression and inflammatory factor levels. In contrast, caveolin-1 siRNA abrogated the protective effects of RSG in the in vitro BBB model of hyperglycemia by increasing TLR4 and Myd88 expression and the levels of inflammatory factors, including TNF-α, IL-1β, and IL-6. Collectively, we demonstrated that hyperglycemia was involved in mediating secondary injury after DAI by disrupting BBB integrity by inducing inflammation through the PPARγ/caveolin-1/TLR4 pathway.

Traumatic brain injury (TBI) is the leading cause of death in young adults and the main cause of mortality and disability across all ages worldwide. We previously analyzed the expression profile data of TBI models obtained from the Gene Expression Omnibus (GEO) database and found that the seripina3n mRNA was markedly upregulated in the acute phase of TBI in four mRNA expression profile data sets, indicating that serpina3n may be involved in the pathophysiological process of TBI. Therefore, we further investigated the biological role and molecular mechanism of serpina3n in traumatic brain injury in this study. As a result, the endogenous level of sepina3n was markedly elevated in the cortex around the contusion sit in mice at day 1 and day 3 after TBI. Inhibiting the expression of serpina3n caused aggravation of neutrophil elastase (NE) expression, BBB disruption, and neurological deficit. With the inactivation of NE, even if serpina3n was silenced, the disruption of the BBB was not further aggravated. In vitro experiments further proved that recombinant serpina3n dose-dependently inhibited the activity of recombinant NE. Based on the above, this study demonstrated that the endogenous level of sepina3n was significantly elevated in the cortex around the contusion sit after TBI in mice, which reduced the secondary blood-brain barrier disruption by inhibiting the activity of neutrophil elastase.

Traumatic brain injury (TBI) causes substantial mortality and long-term disability worldwide. TGFβ1 is a unique molecular and functional signature in microglia, but the role of TGFβ1 in TBI is not clear. The purpose of this study was to investigate the role of TGFβ1 in TBI. The weight dropping device was used to establish TBI model of rats. Hematoxylin eosin staining and Bielschowsky silver staining were used to assess tissue loss. Beam walking and muscle strength tests were used to assess neurological deficits. Immunohistochemical staining was used to assess axonal injures. Western blotting was used to detect expression of related proteins. RT-PCR was used to detect expression of cytokines. Immunofluorescence staining was used to assess the microglia/macrophages activation. We observed obvious axonal injury and microglia/macrophages activation in the peri-lesion cortex. The expression of inflammatory cytokines was markedly high after TBI. The expression of TGFβ1 and TGFβRI were significantly reduced after TBI. TGFβ1 promoted the functional recovery and alleviated axonal injury 1 day after TBI. TGFβ1 promoted microglia/macrophages polarizing to alternative activation and alleviated neuroinflammation. These effects of TGFβ1 could be inhibited by LY2109761, the inhibitor of TGFRI/II. These results suggested that TGFβ1 played a protective role in axonal injury and could be a potential therapeutic target in early stages following TBI.

Increasing evidence has revealed that neuroinflammation plays a pivotal role in axonal injures. Nucleotide oligomerization domain (NOD)-like receptor protein (NLRP3) inflammasome is reported to be widely involved with the pathology of central nervous system disorders. But the role of NLRP3 in diffuse axonal injury (DAI) are rarely reported. The purpose of this study was to investigate the expression of NLRP3 after diffuse axonal injury and the role of NLRP3 in axonal injures. The lateral head rotation device was used to establish DAI model of rats. Immunohistochemical staining for β-amyloid precursor protein and Bielschowsky silver staining were used to assess axonal injures and axonal loss. Terminal Deoxynucleotidyl Transferase-Mediated Digoxigenin-dUTP-Biotin Nick-End Labelling Assay was used to detect cell apoptosis. Brain water content was used to assess cerebral edema and the modified Neurologic Severity Score was used to assess the neurological deficits. Components of NLRP3 inflammasome, such as NLRP3, apoptosis-associated speck-like (ASC) adapter protein and caspase-1, and pro-inflammatory cytokines, for example IL-18 and IL-1β, were over-expressed in early stages of DAI. MCC950, a selective small-molecule inhibitor of NLRP3 inflammasome, inhibited the over-expression of NLRP3 inflammasome and pro-inflammatory cytokines after DAI. MCC950 alleviated axonal injures and cell apoptosis. MCC950 also decreased brain water content and alleviated neurologic deficits 1 day and 3 days after DAI but not 7 days after DAI. These results suggest that MCC950 treatment in the early stages of DAI has a time limiting effect in preventing from axonal injuries and neurological deficits, and that NLRP3 inflammasome plays an important role in axonal injures and may be a potential candidate for axonal injures following DAI.

Objective:To explore the application value of electromagnetic navigation technique in the removal of hematoma under neuroendoscope.Methods:Forty-three patients with supratentorial spontaneous cerebral hemorrhage, accepted removal of hematoma under neuroendoscope in our hospital from October 2015 to February 2019, were chosen in our study; 22 patients (navigation group) were performed the removal under the guide of real-time electromagnetic navigation, and 21 (non-navigation group) were performed the removal under neuroendoscope only. The amount of cerebral hemorrhage, operation time, residual amount of hematoma and hematoma clearance rate were compared between the two groups. Fugl-Meyer Assessment (FMA) was used to evaluate the motor function of the affected limbs two weeks after surgery. The anisotropy fraction (FA) values of fibers of affected pyramidal tracts and contralateral pyramidal tracts were examined by diffusion tensor imaging (DTI), and the relative FA (rFA) value (FA values of affected side/contralateral side) was calculated. Barthel index was used to evaluate the basic daily activities of the patients 6 months after surgery.Results:There was no significant difference between the navigation group and the non-navigation group in the amount of cerebral hemorrhage before surgery, amount of residual hematoma after surgery, hematoma clearance rate, and operation time ( P>0.05). FMA scores of upper and lower limbs, FA and rFA values of the affected side in the navigation group were significantly higher than those in the non-navigation group two weeks after surgery ( P<0.05). Barthel index of patients in the navigation group was statistically higher than that of the non-navigation group 6 months after surgery ( P<0.05). Conclusion:Electromagnetic navigation technique can guide endoscopy to effectively clear the supratentorial hypertensive cerebral hemorrhage without obviously increasing the operation time; effective protection of pyramidal fibers can improve the prognoses of patients.

Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke, but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported. A rat model of traumatic brain injury was established by weight-drop method. The tissue plasminogen activator inhibitor neuroserpin (5 μL, 0.25 mg/mL) was injected into the lateral ventricle. Neurological function was assessed by neurological severity score. Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining. Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay. Apoptotic marker cleaved caspase-3, neuronal marker neurofilament light chain, astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining. Apoptotic cell types were detected by immunofluorescence double labeling. Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining. Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining. Expression of tissue plasminogen activator was increased at 6 hours, and peaked at 3 days after traumatic brain injury. Neuronal apoptosis and axonal injury were detected after traumatic brain injury. Moreover, neuroserpin enhanced neuronal apoptosis, neuronal injury and axonal injury, and activated microglia and astrocytes. Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury. Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury, and activates microglia and astrocytes. This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015.

Blood-brain barrier (BBB) disruption exacerbates diffuse axonal injury (DAI), but the underlying mechanisms are not fully understood. Inactivation or deletion of erythropoietin-producing hepatoma (EPH) receptor A2 (EphA2) attenuated BBB damage and promoted tight junction formation. In this study, we aimed to investigate the role of EphA2 in the protection of BBB integrity and the relevant mechanisms involved in a rat model of DAI. Blocking activation of the EphA receptor by EphA2-Fc ameliorated axonal injury, cell apoptosis, and glial activation, protected BBB integrity and increased expression of the tight junction-associated proteins ZO-1, claudin-5 and occludin-1. In vitro BBB models established by human brain microvascular endothelial cells (HBMECs) were subjected to oxygen deprivation (OGD). Treatment with EphrinA1, which activates EphA2, exacerbated the OGD-induced destruction of permeability and integrity of the BBB models by reducing the expression of tight junction-associated proteins. However, inhibition of Rho-associated coiled coil-containing protein kinases 1 and 2 (ROCK1 and 2) abrogated all of the effects of EphrinA1 on the BBB models in vitro. In conclusion, we provide evidence that EphA2 plays an important role in the destruction of BBB integrity by decreasing the expression of tight junction proteins through the ROCK pathway.

OBJECTIVE:This study aimed to explore the association between genetic variations of CYP19A1 and stroke susceptibility in the Chinese Han population.METHODS:A total of 477 stroke patients and 480 healthy controls were recruited in this study. The genotyping of CYP19A1 polymorphisms (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) was performed by the Agena MassARRAY platform. Under logistic regression models, we evaluated the associations of CYP19A1 polymorphisms and stroke susceptibility by odds ratio and 95% confidence interval.RESULTS:Our study showed that rs4646 (codominant: P = 0.020; recessive: P = 0.016) and rs17601876 (allele: P = 0.044; codominant: P = 0.011; dominant: P = 0.009; recessive: P = 0.046) significantly decreased the risk of stroke. In the stratification analysis, rs4646 is associated with decreased stroke risk among the individuals older than 64 years (codominant: P = 0.028; recessive: P = 0.010) and women (codominant: P = 0.029; recessive: P = 0.029), whereas rs1062033 increased stroke risk in the subgroup of age 64 years and younger (recessive: P = 0.042). The rs17601876 polymorphism has a strong relationship with stroke susceptibility, which is age and gender dependent. In haplotype analysis, we found a block (rs17601876 and rs3751599), and Ars17601876Grs3751599 haplotype is related to an increased stroke risk (P < 0.05). In addition, CYP19A1 variations had effects on clinical characteristics.CONCLUSION:CYP19A1 polymorphisms were significantly associated with stroke susceptibility in the Chinese Han population.

Title: Genetic Variants in CYP4F2 were Significantly Correlated with Susceptibility to Ischemic Stroke Authors: Yuan Wu (yiyi7229@163.com) Junjie Zhao (zhaojunjie_2009@126.com) Yonglin Zhao (zhaoyonglinlin@163.com) Tingqin Huang (guge88@qq.com) Xudong Ma (747001758@qq.com) Honggang Pang (646613359@qq.com) Ming Zhang (zhangming_361@163.com) Version: 3 Date: 30 Aug 2019 Author’s response to reviews: Dear Editors, On behalf of my co-authors, we thank you very much for giving us an opportunity to revise our manuscript, we appreciate you very much for your formatting changes on our manuscript entitled “Genetic Variants in CYP4F2 were Significantly Correlated with Susceptibility to Ischemic Stroke” (ID: MGTC-D-19-00166R3). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and made correction. We hope meet with approval. We have carefully read the editor’s critical suggestions and revised the manuscript point-bypoint. Revised portion are marked using the track changes mode in the marked manuscript.

Traumatic brain in jury affects a number of individuals per year and is a major cause of worldwide death and disability. Yet, its pathophysiological mechanism remains unclear. It is well-known that glial cells, including microglia and astrocytes, are activated and involved in tissue damage and repair in the peri-lesion regions after traumatic brain injury; however, global glial responses are rarely reported. The purpose of this study was to investigate the global activation of microglia and astrocytes 1 day after traumatic brain injury. To test this, we used a weight drop device to inflict traumatic brain injury on left side of the brain and performed hematoxylineosin staining to detect tissue damage. We used immunohistochemical staining and western blotting to detect the activation of microglia and astrocytes 1 day after TBI. We found that microglia were significantly activated in ipsilateral regions. Interestingly, we found that astrocytes were also significantly activated in the ipsilateral regions, contralateral cortex, and contralateral corpus callosum. These results suggest that a focal damage can cause a global glial reaction.

Background Ischemic stroke (IS) is a serious cardiovascular disease and is associated with several single nucleotide polymorphisms (SNPs). However, the role of Cytochrome P450 family 4 subfamily F member 2 ( CYP4F2 ) gene in IS remains unknown. Our study aimed to explore whether CYP4F2 polymorphisms influenced IS risk in the Han Chinese population. Methods We selected 477 patients and 495 controls to do a case-control study, and five SNPs in CYP4F2 gene were successfully genotyped. And we evaluated the associations using the Chi-squared test, independent sample t test, and genetic models analyses. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results In this study, rs12459936 and rs3093144 were associated with IS risk in the overall. After stratified analysis by age (> 61 years), rs3093193 and rs3093144 were related to an increased risk of IS, whereas rs12459936 was related to a decreased risk of IS. In addition, we found that three SNPs (rs3093193, rs3093144 and rs12459936) were associated with the susceptibility to IS in males. We also found five SNPs in the CYP4F2 gene had strong linkage. Conclusions Three SNPs (rs3093193, rs3093144 and rs12459936) in the CYP4F2 were associated with IS risk in a Chinese Han population. And, CYP4F2 gene may be involved in the development of IS.