炎症因子与急性脑梗死的相关性研究

目的 探讨急性脑梗死患者血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和高敏C反应蛋白(hs-CRP)水平的变化及其与脑梗死体积的关系。方法 收集99例急性脑梗死患者(发病时间≤24h)为脑梗死组,40例门诊健康体检正常者为对照组,采用ELISA法测定IL-6、TNF-α、hs-CRP水平,分析其与脑梗死体积的相关性。结果 脑梗死组血清IL-6、TNF-α、hs-CRP水平均显著高于对照组(P0.01);与中等体积梗死组和小体积梗死组相比,大体积梗死组血清IL-6、TNF-α、hsCRP水平均显著增高(P0.01),且三者均与梗死体积呈正相关关系。结论 检测血清IL-6、TNF-α、Hs-CRP水平有助于脑梗死的早期诊断和梗死体积的判断.     

脑梗死后抑郁与血清细胞因子的相关性

目的 探讨血清细胞因子白细胞介素-2 (IL-2)、白细胞介素-6 (IL-6)和肿瘤坏死因子-α(TNF-α)与脑梗死后抑郁的相关性.方法 采用酶联免疫吸附法(ELISA),检测26例脑梗死对照组及28例脑梗死后抑郁组患者血清IL-2、IL-6及TNF-α水平.结果 脑梗死后抑郁组血清IL-2、IL-6和TNF-α水平显著高于对照组;重度抑郁组血清IL-2、IL-6及TNF-α水平显著高于轻度抑郁组.结论 IL-2、IL-6和TNF-α可能在脑卒中后抑郁的发病机制中起重要作用.     

IL-10 TNF-αCRP在急性脑梗死患者血清中的表达及临床意义

目的探讨白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)以及C反应蛋白(CRP)在急性脑梗死患者血清中的表达及临床意义。方法选择2014-01—2016-05驻马店市中心医院收治的急性脑梗死患者67例为患者组,同时选择同期来院体检的健康人群53例为对照组,比较2组患者血清IL-10、TNF-α以及CRP水平,并分析患者组血清IL-10、TNF-α、CRP水平与梗死面积大小的关系。结果患者组血清IL-10、TNF-α、CRP含量均明显高于对照组(P0.05)。在患者组中,血清IL-10、TNF-■、CRP水平随着患者脑梗死面积的增大而增加,且脑梗死大面积者血清IL-10、TNF-α、CRP水平,均明显高于脑梗死小面积者、中等面积者(P0.05),但脑梗死小面积者与中等面积者血清IL-10、TNF-α、CRP水平比较差异无统计学意义(P0.05)。结论血清IL-10、TNF-α、CRP参与急性脑梗死的发生及发展,梗死面积越大,IL-10、TNF-α、CRP水平越高。通过血清IL-10、TNF-α、CRP水平检测有益于急性脑梗死的诊断及预后的评价。     

急性脑梗死与高敏C反应蛋白等相关性炎症因子的临床研究

目的探讨急性脑梗死与高敏C反应蛋白(hs-CRP)以及其他相关性炎症因子的关系。方法选取2012-01—2014-12我院收治的急性脑梗死患者186例为观察组,同期在参加体检的健康者186例为对照组,观察比较2组的基线hsCRP、炎症因子白介素IL-6、IL-8以及肿瘤坏死因子TNFα的水平变化。结果观察组基线hs-CRP水平明显高于对照组,白介素IL-6、IL-8和肿瘤坏死因子TNFα水平变化也较对照组有明显升高,差异均具有统计学意义(P0.05)。结论急性脑梗死患者基线hs-CRP、炎症因子白介素IL-6、IL-8以及肿瘤坏死因子TNFα的水平变化临床表现急剧升高,上述指标的测定对急性脑梗死的预防和治疗具有积极意义。     

急性脑梗死患者同型半胱氨酸与炎症因子的相关性分析

目的研究急性脑梗死患者肿瘤坏死因子-α（TNF-α）及白介素-6（IL-6）与同型半胱氨酸（Hcy）之间的相关性,以探讨其与急性脑梗死发生的关系。方法收集158例急性脑梗死患者（ACI组）、122例健康人（对照组）血液标本,采用循环酶法检测血浆同型半胱氨酸（Hcy）水平,用ELISA法即酶联免疫吸附法测定血清肿瘤坏死因子-α（TNF-α）,白介素-6（IL-6）水平。结果 ACI组Hcy、TNF-α和IL-6的水平均较对照组显著升高（P均〈0.05）。ACI组Hcy与TNF-α、IL-6水平存在显著性正相关（r=0.346,P〈0.05）,TNF-α与IL-6水平之间也存在显著性正相关（r=0.382,P〈0.05）。结论 Hcy、TNF-α、IL-6水平与急性脑梗死的发生密切相关,三者联合检测对急性脑梗死的预防、早期诊断及治疗和预后均有重要价值。     

醒脑静注射液对高血压脑出血患者炎症因子的影响

目的观察醒脑静注射液对高血压脑出血患者炎症因子的影响。方法选取我院神经内科收治的高血压脑出血患者86例,随机分为治疗组46例,对照组40例。2组均给予常规治疗,吸氧、脱水、控制血压、营养脑细胞等对症支持治疗,治疗组在对照组的基础上,加用醒脑静注射液20mL静滴,1次/d,连续治疗14d,观察治疗前后患者血清中C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平变化。结果经14d治疗,治疗组血清CRP水平、TNF-α水平IL-6水平均显著下降,与对照组比较差异有统计学意义(P0.05)。结论醒脑静注射液治疗脑出血疗效显着,可能与降低患者血清CRP、TNF-α和IL-6等炎症因子水平有关。     

脑梗死后癫(癎)患者血清细胞因子水平的改变

目的 研究脑梗死后癫(癎)患者血清细胞因子水平的改变.方法 应用放射免疫法检测87例脑梗死后癫癎患者(脑梗死癫(癎)组)和75名健康体检者(正常对照组)的血清肿瘤坏死因子α(TNF-α),白细胞介素(IL)-2和IL-6水平.结果 脑梗死癫(癎)组血清TNF-α[(2.5±0.57)ng/L]、IL-2[(9.0 4-0.83)ns/L]及IL-6[(97.5±3.1)ng/L]水平明显高于正常对照组[TNF-α(0.89 4-0.36)ng/L,IL-2(4.3±1.5)ng/L,IL-6(13.3 4-11.1)ng/L](均P＜0.01).结论 脑梗死后癫(癎)患者的血清细胞因子TNF-α、IL-2及IL-6水平显著升高,提示细胞因子可能在脑梗死后癫(癎)的发病中起重要作用.     

急性脑梗死患者颈动脉粥样硬化斑块与血液炎症因子水平的关系

目的探讨急性脑梗死患者颈动脉粥样硬化斑块与血液炎症因子水平的关系。方法 164例急性脑梗死患者经颈动脉超声检查分为无斑块组(42例)、稳定斑块组(58例)及不稳定斑块组(64例);其中Ⅰ、Ⅱ、Ⅲ级斑块各为37、45、40例。检测各组患者血清超敏C反应蛋白(hs-CRP)及血浆肿瘤坏死因子-α(TNF-α)、白介素6(IL-6)水平,并进行比较。结果稳定斑块组及不稳定斑块组血清hs-CRP及血浆TNF-α、IL-6水平明显高于无斑块组(均P<0.05);不稳定斑块组明显高于稳定斑块组(均P<0.05)。且随着斑块严重程度的增加,其血清hs-CRP及血浆TNF-α、IL-6水平也明显增高(均P<0.05)。结论血清hs-CRP及血浆TNF-α、IL-6水平可以反映急性脑梗死患者颈动脉粥样硬化的严重程度。     

血必净对颅脑外伤后神经源性肺水肿患者肺功能及血浆TNF-α、IL-6水平的影响

目的 探讨血必净注射液对重型颅脑损伤引起的神经源性肺水肿患者(NPE)肺功能及血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平的影响.方法 将38 例NPE 患者随机分为治疗组和对照组,分别检测两组治疗前、治疗后1 d、4 d、7 d 的血浆TNF-α、IL-6 水平.结果 4 d、7 d 血浆TNF-α、IL-6 水平与对照组比较有显著降低(P ＜0.01).结论 血必净注射液对重型颅脑损伤后神经源性肺水肿(NEP)患者的肺功能有一定的保护作用.     

进展性脑梗死与血清炎性细胞因子白细胞介素-6和肿瘤坏死因子-α的相关性研究

目的探讨血清炎性细胞因子白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)与进展性脑梗死发生发展的相关性。方法采用ELISA方法检测97例急性脑梗死患者(其中进展性脑梗死组37例,非进展性脑梗死组60例)入院后1 d、3 d、5 d、7 d的血清炎性细胞因子IL-6及TNF-α水平和50例正常对照者的IL-6及TNF-α水平,并进行比较。结果进展性脑梗死组各时间点IL-6及TNF-α的浓度均明显高于无进展性脑梗死组及正常对照组(均P0.05)。无进展性脑梗死组各时间点IL-6及TNF-α浓度亦明显高于正常对照组(均P0.05)。结论进展性脑梗死发生发展过程中患者血清炎性细胞因子IL-6及TNF-α水平明显升高,可作为进展性脑梗死的重要血清蛋白标志。     

癫痫持续状态危险因素及神经化学的改变

癫痫持续状态是内科常见的急症,了解其常见的危险因素有利于病因的明确.其发生过程中的神经化学改变如γ氨基丁酸活性的变化,谷氨酸、离子通道及相关炎性因子的改变正逐渐被认识.明确神经化学的变化将有助有癫痫持续状态发病机制的研究和干预手段的改进.     

叶酸受体在中枢神经系统肿瘤中的研究进展

叶酸受体是一种锚着于膜上的糖蛋白,对叶酸具有高度亲和力,在正常组织分布较少,而在多种恶性肿瘤有过度表达,以叶酸受体为作用靶点,使药物与特异性配体结合即可将药物主动靶向肿瘤细胞.本文就叶酸和叶酸受体的组成、生物学特性、在中枢神经系统肿瘤中的分布特点,以及叶酸受体介导主动靶向肿瘤细胞治疗的研究进展进行综述.     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

血浆谷胱甘肽过氧化物酶研究进展

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