Secondary brain injury exacerbates neurological dysfunction and neural cell death following intracerebral hemorrhage (ICH), targeting the pathophysiological mechanism of the secondary brain injury holds promise for improving ICH outcomes. Adjudin, a potential male contraceptive, exhibits neuroprotective effects in brain injury disease models, yet its impact in the ICH model remains unknown. In this study, we investigated the effects of adjudin on brain injury in a mouse ICH model and explored its underlying mechanisms. ICH was induced in male C57BL/6 mice by injecting collagenase into the right striatum. Mice received adjudin treatment (50 mg/kg/ day) for 3 days before euthanization and the perihematomal tissues were collected for further analysis. Adjudin significantly reduced hematoma volume and improved neurological function compared with the vehicle group. Western blot showed that Adjudin markedly decreased the expression of MMP-9 and increased the expression of tight junctions (TJs) proteins, Occludin and ZO-1, and adherens junctions (AJs) protein VE-cadherin. Adjudin also decreased the blood-brain barrier (BBB) permeability, as indicated by the reduced albumin and Evans Blue leakage, along with a decrease in brain water content. Immunofluorescence staining revealed that adjudin noticeably reduced the infiltration of neutrophil, activation of microglia/macrophages, and reactive astrogliosis, accompanied by an increase in CD206 positive microglia/macrophages which exhibit phagocytic characteristics. Adjudin concurrently decreased the generation of proinflammatory cytokines, such as TNF-alpha and IL-1 beta. Additionally, adjudin increased the expression of aquaporin 4 (AQP4). Furthermore, adjudin reduced brain cell apoptosis, as evidenced by increased expression of anti-apoptotic protein Bcl-2, and decreased expression of apoptosis related proteins Bax, cleaved caspase-3 and fewer TUNEL positive cells. Our data suggest that adjudin protects against ICH-induced secondary brain injury and may serve as a potential neuroprotective agent for ICH treatment.

ObjectiveTo explore the relationship between heart rate variability (HRV), the brain distribution of enlarged perivascular space (EPVS), and cognitive impairment in patients with EPVS.Materials and methodsThe clinical and imaging data of 199 patients with EPVS were retrospectively analyzed. EPVS load in the basal ganglia (BG) and centrum semiovale (CS) regions were assessed using the Potter’s method. Cognitive function was evaluated using the Montreal Cognitive Assessment Scale. A logistic regression model was used to analyze the relationship between HRV, the brain distribution of EPVS and cognitive function in patients with EPVS. A receiver operating characteristic curve was used to assess the predictive value of HRV for cognitive function in patients with EPVS.ResultsOf the 199 patients, 27 and 42 presented with severe BG-EPVS and cognitive impairment, respectively. Significant differences were observed in the root mean square of successive differences of normal-normal (NN) intervals for period of interest (rMSSD), the percentage of adjacent NN intervals greater than 50 ms (PNN50), and the ratio of low-frequency power (LF) to high-frequency power (HF) between the mild and severe BG-EPVS groups (P < 0.05). Patients who presented with and without cognitive impairment differed significantly in the standard deviation of NN intervals (SDNN), rMSSD, PNN50, total power, LF, and LF/HF (P < 0.05). rMSSD (odds ratio [OR] 0.871, 95% confidence interval [CI] 0.768–0.988) and LF/HF (OR 3.854, 95% CI 1.196–12.419) were independent influencing factors of BG-EPVS, and rMSSD (OR 0.936, 95% CI 0.898–0.976) was an independent influencing factor of cognitive impairment in patients with EPVS. The optimal cut-off point was 0.312, with an area under the curve of 0.795 (95% CI 0.719–0.872) for predicting cognitive impairment in patients with EPVS by rMSSD.ConclusionReduced HRV is involved in the pathophysiological mechanisms of the formation and development of BG-EPVS and is associated with cognitive impairment in patients with EPVS, independent of CS-EPVS. For patients with HRV changes but without autonomic nervous system symptoms, positive intervention may slow the occurrence or progression of EPVS and cognitive impairment in patients with EPVS.

目的 探究脑小血管病(CSVD)总负荷与急性脑梗死患者早期神经功能恶化(END)的相关性.方法 纳入2018-07-01—2021-10-31郑州大学第二附属医院神经内科治疗的150例急性脑梗死患者,根据是否发生早期神经功能恶化分为END组(n=68)和非END组(n=82),对比2组患者基线资料,包括年龄、性别、吸烟史、饮酒史、既往病史、空腹血糖、血脂四项、同型半胱氨酸、入院时NIHSS评分,并通过头颅MRI评估CSVD总负荷,进行单因素及多因素分析.结果 单因素分析显示,END组空腹血糖、Hcy、NIHSS评分均高于非END组,差异有统计学意义(P<0.05).END组白质高信号(WHM)、血管周围间隙扩大(EPVs)及CSVD总负荷评分高于非END组,差异有统计学意义(P<0.05).多因素Logistic回归分析显示,Hcy(OR=1.119,95％CI=1.001～1.251,P=0.048)、NIHSS评分(OR=2.194,95％CI=1.662～2.895,P<0.001)、CSVD总负荷评分(OR=2.000,95％CI=1.083～3.694,P=0.027)为急性脑梗死患者发生END的危险因素.结论 CSVD总负荷与急性脑梗死患者早期神经功能恶化相关.

Background Cerebral amyloid angiopathy (CAA) is characterized by the deposition of β-amyloid (Aβ) in leptomeningeal vessels and penetrating arterioles. Intracerebral hemorrhage (ICH) is one of the most destructive complications in CAA. Young plasma has been shown to improve cognitive, learning, and memory functions in Alzheimer’s disease (AD) model mice and is a new potential therapy. However, it is not clear whether young plasma can reduce cerebral hemorrhage and improve the prognosis of neurological function in APP/PS1 (which express APP695swe and PS1-dE9 mutations) mice with CAA disease. Methods The Y-maze, new object recognition (NOR), forced swimming, open field, sucrose consumption, and corner tests were used to evaluate the learning and memory, cognitive ability, and emotional changes in CAA model mice. The effect of young plasma on neurogenesis was analyzed by immunofluorescence. The level of Aβ in the cerebral cortex and hippocampus of mice was measured by enzyme-linked immunosorbent assay (ELISA). Finally, the area of cortical hemorrhage in mice was analyzed by fast blue-staining. Results We proved that young plasma improved cognition, learning and memory impairment, and anxiety in CAA model mice, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. However, young plasma did not reduce the level of Aβ in the cortex and hippocampus of APP/PS1 mice. We also found that young plasma reduced the area of cerebral hemorrhage in APP/PS1 mice. Conclusions Our results show that young plasma can improve learning and memory, cognitive impairment, and anxiety in CAA model mice and can reduce the area of cortical hemorrhage.

卒中是造成严重的长期精神和身体残疾的最大原因之一,而卒中后抑郁(post-stroke depression,PSD)是卒中后引起的一种最常见的情绪障碍,严重影响卒中患者的心理健康,降低患者的生活质量,精神错乱可能会对长期预后产生持久的影响,延缓患者的功能恢复,增加复发率和病死率.目前大部分的PSD患者并未得到足够的治疗,其发病机制尚未完全清楚.本文对其流行病学、病因、危险因素、临床表现、诊断和治疗方面作一综述,为PSD的预防和治疗提供参考依据.

目的 分析曲唑酮片联合唑吡坦治疗失眠对睡眠障碍评定量表(SDRS)、匹兹堡睡眠质量指数(PSQI)及多导睡眠图(PSG)的影响.方法 纳入120例于2018-05—2021-10于郑州大学第二附属医院接受治疗的失眠患者,A组40例施予曲唑酮片治疗,B组40例施予唑吡坦治疗,C组40例施予曲唑酮片联合唑吡坦治疗,对比3组SDRS、PSQI评分及PSG各指标.结果 治疗后7 d、14 d、28 d,C组SDRS评分分别为(14.04±5.57)分、(10.15±4.32)分、(7.82±3.62)分,均较A组(18.73±6.41、12.15±5.53、11.37±4.55)、B组(18.32±5.92、12.42±4.37、11.23±4.65)低,差异均有统计学意义(P<0.05);C组PSQI评分分别为(12.29±1.29)分、(12.35±1.04)分、(7.14±0.63)分,均较A组(15.83±1.34、14.32±1.27、12.29±1.29)、B组(15.84±1.43、14.45±1.15、12.35±1.04)低,差异均有统计学意义(P<0.05);C组中PSG睡眠效率、睡眠总时间、醒觉时间、入睡时间(82.53±6.74、389.24±33.34、80.27±32.63、29.24±4.77)各项指标优于A组(74.18±6.83、333.61±34.69、120.53±33.48、36.08±4.17)、B组(73.84±7.03、334.63±35.75、120.63±34.15、35.93±3.84),差异均有统计学意义(P<0.05).结论 失眠患者给予曲唑酮片联合唑吡坦治疗效果显著,有助于改善患者的SDRS、PSQI评分及PSG指标.

[目的]探讨高级别胶质瘤患者谷胱甘肽S-转移酶P-1(glutathione S-transferase P-1,GSTP-1)基因多态性与替莫唑胺联合放疗疗效的相关性.[方法]本研究从2012年1月至2019年12月纳入268例术后接受替莫唑胺联合放疗辅助治疗的高级别胶质瘤患者.通过病例系统获取患者的基线临床资料,以及后期的电话随访获取患者的预后数据,进而分析替莫唑胺联合放疗方案的预后.在患者住院期间收集患者外周血样本进行GSTP-1多态性的基因分型,并结合基线临床资料进行相应的关联分析.此外,收集可用于mRNA表达分析的样本进行GS TP-1基因的表达分析,进而探讨该位点对GSTP-1基因mRNA表达的影响.[结果] 268例患者的中位无进展生存期为7.0个月,中位总生存期为13.5个月.关联分析中只发现了位于GSTP-1基因编码区域的313A＞G位点和预后显著相关.313A＞G位点在研究人群中的分布频率为:AA型182例(67.9％),AG型79例(29.5％),GG型7例(2.6％),最小等位基因频率为0.17,该位点基因型分布频率符合哈迪温伯格平衡(P=0.649).AA基因型和AG/GG基因型患者的中位无进展生存期分别为9.0个月和5.8个月,差异具有显著的统计学意义(x2=14.51,P＜0.001).总生存期方面,AA型和AG/GG基因型患者的中位总生存期分别为15.5个月和10.0个月,差异具有显著的统计学意义(x2=9.53,P=0.002).多因素分析中,针对PFS构建的Cox模型结果表明AG/GG基因型对PFS具有独立的影响(HR=l.56,P=0.005).mRNA分析结果表明在88例外周血单核细胞标本的mRNA表达分析中,313A＞G位点AG/GG基因型患者相对于野生型的AA基因型患者,PBMC标本中GS TP-1的mRNA表达显著较高(P＜0.001).[结论]高级别胶质瘤患者接受替莫唑胺联合放疗的辅助治疗具有和既往研究类似的预后,GSTP-1基因313A＞G多态性位点可能成为评估该方案预后的药物基因组因素.

目的 探讨强直性肌营养不良1型(myotonic dystrophy type 1,DM1)脑白质病变的临床特点和影像学表现,并结合肌肉活检和基因检测,加深对该疾病的认识,避免漏诊及误诊.方法 结合肌肉活检和基因检测的结果,分析1例伴脑白质病变的强直性肌营养不良1型患者的临床特点及影像学表现.结果 患者因"双下肢无力,行走不稳4a"入院,秃顶,面容呈"斧状脸",双眼白内障术后,头颅MRI显示双侧颞叶和脑室旁成高信号,肌电图可见肌强直电位,肌肉活检呈肌营养不良样病理改变,最终经基因检测确诊为DM1.结论 强直性肌营养不良是一组以肌无力、肌强直和肌萎缩为特点的多系统受累的罕见病,通过患者的症状和体征表现,并结合影像学,肌肉活检和基因检测进行诊断.

三叉神经痛的特征表现为单侧阵发性的面部疼痛,疼痛性质通常为针刺或电击样,疼痛范围局限在三叉神经支配区的一支或多支.经典的三叉神经痛被认为由于三叉神经受到血管慢性压迫后出现脱髓鞘或者髓鞘化不良,受损的神经纤维自发异常放电引起烧灼样的痛觉,然而其具体的发病机制仍存在争议.临床试验表明A型肉毒素可以安全有效治疗三叉神经痛,然而其作用机制仍不清楚,与其肌肉麻痹的作用机制相比,其镇痛机制似乎更加复杂.本篇综述回顾了三叉神经痛的发病机制、A型肉毒素的结构、镇痛作用机制以及注射可能带来的不良反应,作用机制部分包括在外周抑制炎性介质的释放、Na通道的失活、抑制瞬时感受器电位(TRP)通道在细胞膜上的表达、逆向轴突转运和转胞吞作用.

Background Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila. Methods Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC). Results Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration. Conclusion The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.

We aimed to investigate the effect of CPEB4 on the apoptosis of brain glioma cells through NOTCH signaling pathway.CPEB4 protein was detected by Western blotting in the human brain glioma tissues and the corresponding adjacent tumor tissues.Human glioma cells U87 served as the research object.CPEB4 siRNA and siRNA control were transfected into U87 cells by cell transfection,while the control group was only added to the transfection reagent.The levels of CPEB4 in cells were detected by Western blotting.Cell apoptosis was detected by flow cytometry.Western blotting was used to determine the levels of NICD1,NICD2,HES1 and Cleaved Caspase-3.Human glioma cells were treated with 20 μmol/L of NOTCH signaling pathway inhibitor S2188 for 48 h,and NICD1,NICD2,Cleaved Caspase-3,HES1 protein levels and the cell apoptosis were measured.The results showed that the levels of CPEB4 protein in human glioma tissues were significantly higher than those in the adjacent tumor tissues(P ＜ 0.01).CPEB4,NICD1,NICD2,HES1,Cleaved Caspase-3 protein and apoptosis rate in siRNA control group had no significant change compared with the control group(P ＞ 0.05).The level of CPEB4 in CPEB4 siRNA group was significantly lower than that in control group(P ＜ 0.01).The cell apoptosis rate and the expression level of Cleaved Caspase-3 in CPEB4 siRNA group were significantly higher than those in control group(P ＜ 0.01).The expression levels of NICD1,NICD2 and HES1 in CPEB4 siRNA group were significantly lower than those in control group(P ＜ 0.01).The apoptosis of human glioma cells after blockage of NOTCH signaling pathway by inhibitor was consistent with the CPEB4 siRNA group.CPEB4 expression was up-regulated in human glioma tissues.Thus,inhibiting the expression of CPEB4 can promote the apoptosis of human glioma cells,and the mechanism is related to the NOTCH signaling pathway.

Objective: This study aimed to explore whether the regulatory effect of miR-21 on alpha-synuclein expression in neurons is a potential mechanism by which geniopside (GP) protects the central nervous system from Parkinson disease (PD).Methods: The human neuroblastoma cell line SH-SY5Y was induced to differentiate in vitro and treated with dimethyl sulfoxide (DMSO), N-methyl-4-phenylpyridinium iodide (MPP+), and MPP+ together with GP. To identify the role of miR-21 in the regulation of lysosome-associated membrane protein 2 (LAMP2A) and alpha-synuclein, SH-SY5Y cells pretreated with MPP+ were transfected with miR-21 mimic and miR-21 inhibitor. To identify whether GP could reduce the level of alpha-synuclein through miR-21/LAMP2A, SHSY5Y cells pretreated with GP were treated with miR-21 mimic or miR-21 inhibitor; meanwhile, a luciferase reporter assay was performed to confirm the direct target of miR-21. LAMP2A was overexpressed using a pCMV6-XL5-LAMP2A vector to confirm the role of LAMP2A in the regulation of alpha-synuclein by miR-21. In these in vitro experiments, the RNA and/or protein expressions of miR-21, LAMP2A, and alpha-synuclein in SH-SY5Y cells were determined by quantitative real-time polymerase chain reaction and/or western blotting, respectively. An in vivo PD mouse model was established through intraperitoneal injection with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). The mice were treated with saline, MPTP, MPTP+GP, and MPTP+GP+miR-21 agomir. The numbers of TH+ cells in the substantia nigra in different groups of mice were compared. The RNA and/or protein expressions of miR-21, LAMP2A, and alpha-synuclein were also determined.Results: The level of miR-21 in the cells or mice models was significantly higher than that in normal cells or normal mice, respectively, and GP significantly downregulated miR-21. GP also raised the protein and mRNA expressions of LAMP2A and reduced the protein level of alpha-synuclein in PD models. MiR-21 upregulated the expression of alpha-synuclein by directly targeting 3' UTR of LAMP2A. LAMP2A overexpression abolished the upregulating effect of miR-21 mimic on alpha-synuclein. MiR-21 mimics/agomir reversed the GP-induced downregulation of alpha-synuclein; miR-21 inhibitor effectively increased the downregulation of alpha-synuclein caused by GP.Conclusion: GP exhibits neuroprotective properties by inhibiting alpha-synuclein expression in PD models through the miR-21/LAMP2A axis. Copyright (C) 2016 Elsevier B.V. All rights reserved.

目的：探讨血清骨桥蛋白（osteopontin ，OPN）水平与脑梗死患者动脉粥样硬化斑块稳定性关系。方法根据颈部彩色多普勒超生检查结果，收集119例急性脑梗死患者，ELISA 法测定不同类型脑梗死组血清OPN水平。结果不同类型脑梗死患者血浆OPN水平之间无明显差异，血栓形成性脑梗死含量明显高于其他梗死组，不稳定斑块组血清OPN水平明显高于稳定斑块组，差异均有统计学意义（P＜0.05）。结论脑梗死患者血浆OPN水平和颈动脉粥样硬化斑块的不稳定性密切相关。血清OPN亦可作为颈动脉易损斑块的生物学标记物。

目的：探讨丙戊酸钠与阿米替林联合治疗原发性头痛的临床疗效。方法对112例原发性头痛患者随机分为治疗组（丙戊酸钠、阿米替林）62例，对照组（加巴喷丁）50例，治疗组给予丙戊酸钠片0.2 g tid po ，同时加用阿米替林25 mg qn po 。对照组给予加巴喷丁0.1 g ，tid po ；疗程均为4周，于治疗前及治疗后4周进行头痛程度评分。结果治疗组头痛缓解的总有效率与对照组相比，差异具有统计学意义（P＜0.05），治疗组疗效明显高于对照组。结论丙戊酸钠联合阿米替林治疗能明显缓解原发性头痛患者临床症状，临床效果安全有效，不良反应较少。

目的 探讨Rho激酶抑制剂法舒地尔对大鼠脑缺血再灌注损伤后的保护作用及可能机制.方法 健康成年雄性SD大鼠90只,随机分为3组:假手术组、模型组、法舒地尔组,每组30只,每组再按照再灌注时间不同分为6、1 2、24 h3个时间点,每个时间点10只,线栓法制作大鼠大脑中动脉缺血再灌注损伤模型.术后对大鼠进行神经功能评分,RT-PCR检测缺血侧脑组织中新型趋化因子mRNA、NF-κB p65 mRNA表达.结果 与假手术组比较,模型组和法舒地尔组大鼠脑缺血再灌注6、12、24 h NF-κB p65 mRNA、新型趋化因子mRNA表达明显升高,差异有统计学意义(P＜0.05)；与模型组比较,法舒地尔组大鼠脑缺血再灌注6、12、24 h神经功能缺损评分明显降低,12、24 h NF-κB p65 mRNA、新型趋化因子mRNA表达明显降低,差异有统计学意义(P＜0.05,P＜0.01).结论 法舒地尔的脑保护作用可能与其减轻大鼠脑缺血再灌注损伤后的炎性反应有关.

目的探讨丁苯酞(Dlbutylphthalide,NBP)对血管性痴呆(VD)大鼠学习记忆功能的影响。方法采用双侧颈总动脉永久结扎法建立大鼠VD模型60只,随机分为假手术组、模型组和丁苯酞组(腹腔注射给予丁苯酞,1次/d,连续4 w),每组20只,用Y迷宫试验观察行为学改变,在RT-PCR水平观察各组海马区HO-1 mRNA的表达变化,HE染色法检测细胞形态变化。结果丁苯酞组学习和记忆成绩显著优于VD组;模型组海马区HO-1 mRNA表达跟假手术组相比明显的增多,丁苯酞组跟模型组比较HO-1 mRNA的表达明显增多,其差异有统计学意义。结论丁苯酞对VD的保护作用可能通过上调脑组织中的HO-1 mRNA的表达而实现。

Objective To study the role of Rho kinase inhibitor(fasudil) in protection of rat myocardium against cerebeal ischemia reperfusion injury and its possible mechanism.Methods Ninety adult healthy male SD rats were randomly divided into sham operation group,model group,and fasudil group(30 in each group).Rats in each group were further divided into 6 h reperfusion group,12 h reperfusion group and 24 h reperfusion group(10 in each group).A rat middle cerebral artery ischemia reperfusion model was established with thread embolism.Nerve function in rats was scored after operation.Levels of novel chemotactic factor mRNA and NF-κB p65 mRNA in ischemic brain tissues were measured by RT-PCR.Results The expression levels of NF-κB p65 mRNA and novel chemotactiv factor mRNA were significantly higher in model group,fasudil group,6 h reperfusion group,12 h reperfusion group and 24 h reperfusion group than in sham operation group(P<0.05),The score of nerve function and the expression level of NF-κB p65 mRNA and novel chemotactic factor mRNA were significantly lower in fasudil group,6 h reperfusion group,12 h reperfusion group and 24 h reperfusion group than in model group(P<0.05). Conclusion The role of fasudil in protection of rats agaist cerebral ischemia reperfusion injury is related with the alleviated inflammatory reaction.