小胶质细胞与缺血性脑卒中的相关研究

缺血性脑卒中是脑卒中常见的类型,是威胁人类健康的重大疾病之一。神经炎性反应被认为是缺血性脑卒中的重要病理机制。小胶质细胞是中枢神经系统常驻免疫细胞,在启动先天和适应性免疫反应中发挥重要作用。小胶质细胞介导的神经炎性反应与缺血性脑卒中的发展及预后密切相关。现就小胶质细胞与缺血性脑卒中的相关性进行综述。     

小胶质细胞在脑出血病理生理学机制中的研究进展

脑出血是临床常见的脑血管病之一,目前尚缺乏有效治疗药物.小胶质细胞是一种特异性存在于中枢神经系统的免疫细胞,脑出血急性期小胶质细胞迅速激活并在M1型与M2型之间动态转变,提示小胶质细胞在脑出血后继发性神经炎症反应的病理生理学过程中具有复杂的作用机制,成为探究脑出血治疗药物的重要靶点.本文对脑出血后小胶质细胞表面标志物、...     

衰老小胶质细胞形态功能改变在帕金森病发病机制中的研究进展

帕金森病（Parkinson disease, PD）是一种衰老相关的神经退行性疾病,其发病机制尚不明确。已有研究表明小胶质细胞参与的神经炎症反应可能是PD发病的关键因素,但衰老小胶质细胞对PD发病及疾病进展的潜在影响尚未阐明。本文总结了衰老小胶质细胞在形态和功能方面的变化,并指出这些变化产生的促炎作用,分析了PD相关危险因素对小胶质细胞的衰老损害,初步探讨衰老小胶质细胞介导免疫失衡机制在PD的疾病过程中发挥的致病作用,并对靶向衰老小胶质细胞的潜在治疗手段进行简要综述。     

小胶质细胞在酒精依赖中的研究进展

近年来,神经炎症在成瘾行为中的细胞和分子机制逐渐凸显,酒精滥用直接或间接与神 经免疫系统相互作用,产生中枢免疫信号,改变神经免疫基因表达和信号转导,进而导致成瘾。小胶质 细胞是中枢神经系统（CNS）中神经免疫应答和炎症的主要调节剂,现回顾有关长期酒精暴露与小胶质 细胞激活的研究,突出小胶质细胞在CNS 酒精反应中起到的关键监管作用,对于开发更好的治疗酒精 依赖的方案至关重要。     

小胶质细胞在癫痫发作状态中的研究进展

癫痫是一组由于脑部神经元异常过度放电引起的中枢神经系统疾病。小胶质细胞作为中枢神经系统的主要免疫细胞对神经的发育和维持起着重要作用。尽管研究报道,小胶质细胞可通过增加炎症介质等生物活性物质介导癫痫发作,但对于炎症介质相关的信号转导通路仍缺乏全面了解。此外,越来越多的证据证明,小胶质细胞在神经元变性、神经发生及突触修剪中发挥着至关重要的作用,这与癫痫的发生发展有关。因此,进一步研究小胶质细胞在癫痫发作过程中的生物学功能,明确小胶质细胞在癫痫中的分子机制,可为临床治疗癫痫提供新的分子靶点。 [国际神经病学神经外科学杂志, 2023, 50(6): 57-62]     

小胶质细胞极化在肌萎缩侧索硬化发病中的作用研究进展

肌萎缩侧索硬化(amyotrophic lateral sclerosis, ALS)是一种神经系统慢性进行性变性疾病,其病因及发病机制仍不明确。越来越多证据表明,免疫异常及神经炎症与ALS的发病密切相关,其中小胶质细胞的极化作为神经炎症研究重要组成部分,其与ALS发病及进展密切相关,深入研究小胶质细胞极化在ALS中的作用机制可能为ALS的临床诊断、靶向干预治疗提供线索和思路。现就小胶质细胞极化在ALS发病中的作用研究进展进行综述。     

小胶质细胞在阿尔茨海默病发病中的作用研究进展

阿尔茨海默病（Alzheimers disease,AD）是一种以进行性认知障碍和记忆力损害为主要表现的中枢神经系统（center nervous system,CNS）退行性病变。     

小胶质细胞在癫痫中作用的研究进展

正癫痫是神经元突发、异常、过度、同步放电引发的一种发作性脑功能障碍。癫痫发病机制十分复杂。研究发现神经炎症、氧化应激、免疫失调、神经元凋亡、自噬等因素,在癫痫发病过程中发挥重要作用。小胶质细胞是中枢神经系统的免疫效应细胞,参与将神经炎症、氧化应激、神经元凋亡、免疫调节等。本文就小胶质细胞在癫痫中的作用进行综述。1小胶质细胞的概述1.1小胶质细胞的类型与功能小胶质细胞外形和蛋白表达存在差异,不同条件激活的类型和功能状态也有差异[1]。小胶质细胞处于静息状态时体积较小,呈梭状,有树枝状分支;激活后,细胞体积变大,     

小胶质细胞在缺血性脑卒中中作用机制的研究进展

正脑卒中是导致人们死亡和残疾的重要疾病之一,可分为缺血性和出血性脑卒中,其中缺血性脑卒中占绝大部分,并且由于缺血造成的一系列的反应会造成神经元的功能失调以及死亡~([1]),同时也可能破坏血脑屏障造成进一步的脑水肿与炎症反应~([2]),使病情进一步恶化。在缺血性脑卒中的病理机制中,炎症反应发挥着重要的作用。缺血性脑卒中之后,脑内固有的小胶质细胞被活化~([3])。最初研究认为小胶质细胞在急性期会加剧脑组织的损伤~([4]),但是随着研究的深入,     

胶质细胞在癫痫发病机制中的作用研究进展

癫痫是神经系统疾病中的一种严重危害人类健康的常见病、多发病，患病率约为1％，发病机制非常复杂。胶质细胞是神经系统的重要组成部分，胶质细胞占脑细胞总数的约90％，包括星形胶质细胞、少突胶质细胞和小胶质细胞，其在生理与病理状态下对维护神经系统功能的作用至今未明。胶质细胞不仅与脑的正常生理活动、发育以及神经病理过程有明显关系，而且与神经元的功能活动以及损伤与修复过程有千丝万缕的联系。近年来研究表明胶质细胞在癫痫的发病机制中扮演重要角色。本文就痫性发作时胶质细胞功能改变（细胞形态改变、免疫表型改变和细胞增殖活动）、胶质细胞与神经元之间物质、信息交流方面的研究进展进行综述。     

脑出血损伤相关分子模式研究进展

脑出血后产生的免疫风暴可导致神经元及其支持细胞死亡,红细胞裂解释放的血红蛋白、血红素和铁离子等细胞毒性物质也具有促进神经细胞死亡的作用。神经细胞死亡后释放的损伤相关分子模式(DAMP)激活固有免疫反应,导致炎症反应-细胞死亡-DAMP释放-炎症反应的恶性循环,是脑出血后继发性脑损伤的重要机制。本文旨在对目前开展的一系列探讨DAMP在脑出血继发性脑损伤中作用的研究进展进行概述,以为进一步的基础研究与临床转化研究提供参考。     

NLR与脑出血预后关系的研究进展

脑出血具有病残率高和病死率高的特点。炎性反应与脑出血病程密切相关，脑出血后白细胞释放炎性介质与细胞毒性介质，通过提高毛细血管通透性、促进细胞肿胀，损伤血脑屏障，进而增强病变周围水肿，影响脑出血的临床病程。因此，炎症标志物有助于判断脑出血发展过程及预后。在炎症反应中，中性粒细胞和淋巴细胞是两类主要参与者，中性粒细胞与淋巴细胞比值（NLR）则整合了这两类细胞的信息，是炎症反应的可靠指标，该比值在临床应用中存在一定的潜在价值。本文结合相关研究，重点阐述NLR在脑出血后发展过程中的相关作用机制及对预后评估的意义。     

Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage

Proteases, such as tissue plasminogen activator, thrombin, metalloproteinases, and cathepsins, have complex functions in the mammalian brain under both normal and pathological conditions. Some of these proteases are expressed by neuronal cells, whereas others are made by the immunocompetent, macrophage-like cells of the brain: the microglia. This article reviews the physiological and pathological functions of these proteinases in the brain as well as recent findings linking extracellular proteases with neuronal cell death in ischemic or hemorrhagic stroke. Better understanding of protease expression and signaling, microglial activation, and their relationship with neuronal cell death during stroke injury could contribute to the development of relevant inhibitors as novel neuroprotective agents for treating ischemic stroke and intracerebral hemorrhage.     

Protective role of TLR9‐induced macrophage/microglia phagocytosis after experimental intracerebral hemorrhage in mice

IntroductionIntracerebral hemorrhage (ICH) causes devastating morbidity and mortality, and studies have shown that the toxic components of hematomas play key roles in brain damage after ICH. Recent studies have found that TLR9 participates in regulating the phagocytosis of peripheral macrophages. The current study examined the role of TLR9 in macrophage/microglial (M/M) function after ICH.MethodsRAW264.7 (macrophage), BV2 (microglia), and HT22# (neurons) cell lines were transfected with lentivirus for TLR9 overexpression. Whole blood from C57BL/6 or EGFP^Tg/+ mice was infused for phagocytosis and injury experiments, and brusatol was used for the experiments. Intraperitoneal injection of the TLR9 agonist ODN1826 or control ODN2138 was performed on days 1, 3, 5, 7, and 28 after ICH to study the effects of TLR9 in mice. In addition, clodronate was coinjected in M/M elimination experiments. The brains were collected for histological and protein experiments at different time points after ICH induction. Cellular and histological methods were used to measure hematoma/iron residual, M/Ms variation, neural injury, and brain tissue loss. Behavioral tests were performed premodeling and on days 1, 3, 7, and 28 post‐ICH.ResultsOverexpression of TLR9 facilitated M/M phagocytosis and protected neurons from blood‐derived hazards in vitro. Furthermore, ODN1826 boosted M/M activation and phagocytic function, facilitated hematoma/iron resolution, reduced brain injury, and improved neurological function recovery in ICH mice, which were abolished by clodronate injection. The experimental results indicated that the Nrf2/CD204 pathway participated in TLR9‐induced M/M phagocytosis after ICH.ConclusionOur study suggests a protective role for TLR9‐enhanced M/M phagocytosis via the Nrf2/CD204 pathway after ICH. Our findings may serve as potential targets for ICH treatment.     

Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages

OBJECTIVE: Phagocytosis is necessary to eliminate the hematoma after intracerebral hemorrhage (ICH); however, release of proinflammatory mediators and free radicals during phagocyte activation is toxic to neighboring cells, leading to secondary brain injury. Promotion of phagocytosis in a timely and efficient manner may limit the toxic effects of persistent blood products on surrounding tissue and may be important for recovery after ICH. METHODS: Intrastriatal blood injection in rodents and primary microglia in culture exposed to red blood cells were used to model ICH and to study mechanisms of hematoma resolution and phagocytosis regulation by peroxisome proliferator-activated receptor gamma (PPARgamma) in microglia/macrophages. RESULTS: Our study demonstrated that the PPARgamma agonist, rosiglitazone, promoted hematoma resolution, decreased neuronal damage, and improved functional recovery in a mouse ICH model. Microglia isolated from murine brains showed more efficient phagocytosis in response to PPARgamma activators. PPARgamma activators significantly increased PPARgamma-regulated gene (catalase and CD36) expression, whereas reducing proinflammatory gene (tumor necrosis factor-alpha, interleukin-1beta, matrix metalloproteinase-9, and inducible nitric oxide synthase) expression, extracellular H(2)O(2) level, and neuronal damage. Phagocytosis by microglia was significantly inhibited by PPARgamma gene knockdown or neutralizing anti-CD36 antibody, whereas it was enhanced by exogenous catalase. INTERPRETATION: PPARgamma in macrophages acts as an important factor in promoting hematoma absorption and protecting other brain cells from ICH-induced damage.     

脑小血管病对自发性脑出血发病及预后影响的研究进展

脑小血管病主要影响脑内小动脉、微动脉、毛细血管及小静脉等，与脑出血的发病与预后密切相关，具体包括脑出血的发生、出血部位、出血体积、出血后再发卒中、出血后功能结局、总体生存期等。现对脑小血管病对自发性脑出血的发病及预后的影响的研究进展进行综述，为临床实践提供参考。     

Spontaneous supratentorial intracerebral hemorrhage: the role of surgical management

Spontaneous supratentorial intracerebral hemorrhage is a vexing clinical problem. Without established guidelines, clinicians are often forced to make case-by-case decisions, based on their own interpretation of relevant studies and experience. A number of randomized studies and several meta-analyses have been unable to provide a clear indication for surgery for this condition. Data from both experimental and clinical studies suggest that early surgical evacuation in some circumstances may be beneficial. This may include a subset of patients with moderate sized hemorrhages and associated moderate neurological deficits; specifically those patients that are likely to survive the primary bleed but with significant permanent neurological deficits. Minimal access surgical techniques may offer advantages over standard large craniotomies, although a role for stereotactic aspirations has not yet been established. The timing of any surgery may also be important with theoretical advantages associated with early and thorough clot evacuation. Future surgical advances will require techniques or adjuvant medical treatment to reduce the occurrence of clot expansion and rebleeding, that have been identified as a source of early deteration and post-operative condition. We review the randomized clinical trials, experimental evidence and management options related to surgical treatment of spontaneous supratentorial intracerebral hemorrhage.     

骨髓间质干细胞治疗脑出血的研究进展

目的 骨髓间质干细胞在骨髓间质中含量丰富,具有很强的自我复制和分化能力.经过一系列提取与培养,其可通过脑室、动脉、静脉等不同途径移植于脑出血模型,从而为脑出血的治疗开辟新的路径.