Abstract: Many endogenous, exogenous and systemic factors individually can lead to occlusive vessel pathology affecting the neuroendovascular unit compromising cerebral blood flow. The brain ischemia thus created irrespective of the pathology has similar endpoint and involves blood vessels, astrocytes, neurons and surrounding microglia triggering the whole spectrum of neuroinflammation which is an important component in the ischemic cascade. The resultant series of neuroinflammatory reactions cause depolarization of neuronal cells and activation of pro-inflammatory cellular agents and subsequently cell death. Neuroinflammation can be an effect and (or) cause of acute energy failure, excitotoxicity, ionic imbalance, channel dysfunctions, and oxidative free radicals in the central nervous system. Non-restoration of the blood flow within the threshold period can result in an extensive brain damage from activation of deadly latent proteases like matrix metalloprotease, and immediate early genes destroying the neuronal microenvironment and blood brain barrier. It is paradoxical that both deoxygenation and reoxygenation can contribute significantly to the stroke neuroinflammatory injury. The cascade of cerebral injury also involves activation of microglia and astrocytes leading to release of chemical mediators like cytokines, oxygen free radicals, neurotoxic and neurotropic factors further contributing to the damage. Neutrophil activation and binding to endothelial surface using adhesion molecules and their subsequent transmigration to the ischemic core will enhance the injury. Monocyte and macrophage will also play a role in brain injury by its release of cytokine and transformation into phagocytes. Strategy to target various players of neuroinflammation to halt or minimize the cerebral damage concentrate on inhibiting intracellular adhesion molecules (ICAMs), vascular cell adhesion molecules (VCAMs), neutrophils, microglia, major histocompatibility complex (MHC), cytokine, chemokine and free radical scavenger system. Different strategies to suppress inflammation secondary to ischemia have shown promise in experimental environment but have failed to demonstrate successful clinical translation and further studies are underway. However, this knowledge of neuroinflammation becomes crucial in developing novel therapies for neuroprotection and broadening the field of therapeutic options for cerebral ischemia which is currently limited. In this brief review we try to address diverse mechanisms involving neuroinflammation in relation to ischemic stroke.

Key words: Brain ischemia, Inflammation, Central nervous system, Immunity, celluar, Neuroimmunomodulation, Review

摘要： 各种内源性、外源性和系统性因素均可影响脑血流的神经血管内单位，但又互为导致血管闭塞的独立因素。无论何种机制引起的脑缺血，其结局均相同，包括血管因素、星形胶质细胞、神经元和诱发神经炎症疾病谱的周围小胶质细胞。而神经炎症反应则为缺血级联反应中的重要环节，可引起神经细胞去极化和炎性细胞因子前体激活，继而细胞死亡。神经炎症反应可引起中枢神经系统急性能量衰竭、兴奋性毒性反应、电解质紊乱、离子通道功能障碍和氧自由基分泌增多等一系列反应，而又可以是其后果。若在阈值期内缺血状态不能得到改善，则可激活基质金属蛋白酶，导致脑组织广泛损害，而即早基因激活将致使神经体液微内环境和血?脑脊液屏障破坏。脱氧和复氧均可造成卒中相关性损伤。缺血性脑损伤级联反应的病理过程还包括小胶质细胞和星形胶质细胞活化，释放细胞因子、氧自由基、神经毒性因子和神经营养因子等化学介质，进一步加重脑损伤。与此同时，中性粒细胞活化并通过细胞内黏附因子结合到内皮细胞表面，然后移行至缺血核心区，加剧脑组织损伤。单核细胞和巨噬细胞通过释放炎性细胞因子和转化为吞噬细胞而在缺血性脑损伤过程中发挥作用。针对神经炎症不同环节的治疗原则，是停止或减轻脑损伤程度，如抑制细胞内黏附分子（ICAMs）、血管细胞黏附分子（VCAMs）、中性粒细胞、小胶质细胞、主要组织相容性复合物（MHC）、细胞因子、趋化因子和自由基活性。上述针对脑缺血后神经炎症的各种治疗方法，动物实验已有可喜的结果，但临床试验未见成效，目前正在做进一步研究。然而，了解神经炎症的病理学机制，对今后开发新型神经保护治疗方法的开拓脑缺血治疗领域至关重要。本文旨在阐述缺血性卒中相关神经炎症反应的不同病理学机制。

关键词: 脑缺血, 炎症, 中枢神经系统, 免疫, 细胞, 神经免疫调节, 综述