The role of cytokines in the neuropathology of stroke and neurotrauma
The role of cytokines in the neuropathology of stroke and neurotrauma
复制标题
DOI：
10.1159/000026331
复制
发表时间：
1998-05-01
影响因子：
2.4
通讯作者：
Barone, FC
中科院分区：
文献类型：
--
作者：
Feuerstein, GZ;Wang, XK;Barone, FC
在过去的十年中，越来越多的证据表明，中枢神经系统可以对包括创伤、缺血、移植、病毒感染和神经变性在内的各种侮辱产生明确的炎症反应。这种中枢派生的炎症反应的许多方面在某种程度上与外周的这种反应的性质相似。通过分子遗传学技术的应用，包括聚合酶链式反应，结合高特异性抗体的可获得性，利用cDNA探针，关于脑损伤发生的分子机制的新概念正在迅速涌现。特别是，细胞因子，特别是肿瘤坏死因子α和白介素1β在中枢神经系统炎症反应的传播和维持中的重要性被强调。这篇综述总结了支持缺血和创伤在受损的脑组织中引起炎症状态的证据。炎症状态由细胞(脑损伤后早期的中性粒细胞和随后的单核细胞浸润)和介质(细胞因子、趋化因子和黏附分子)组成。很明显，在局灶性缺血和创伤后不久和组织损伤发展的时候，脑组织中促炎症细胞因子、趋化因子和内皮-白细胞黏附分子的从头上调发生。炎症反应的重要性及其对脑损伤的贡献现在得到了更好的理解。已有证据支持细胞因子在驱动炎症反应中的作用，并且这一过程与脑损伤的程度有因果关系。综述的证据包括：(1)特定细胞因子加重脑损伤的能力；(2)特定细胞因子阻断减少缺血性脑损伤的能力；(3)循环中性粒细胞的耗竭减少缺血性脑损伤；(4)内皮细胞-白细胞黏附相互作用的拮抗剂(如抗ICAM-1)减少缺血性脑损伤。靶向驱动大脑对损伤的炎症反应的细胞因子为中风和神经创伤的新疗法干预提供了机会。
Accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory reaction to a variety of insults including trauma, ischemia, transplantation, viral infections as well as neurodegeneration. Many aspects of this centrally derived inflammatory response parallel to some extent the nature of such a reaction in the periphery. Through the recent application of molecular genetic techniques including PCR, utilization of cDNA probes in conjuncture with the availability of highly specific antibodies, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNF alpha and IL-1 beta, is emphasized in the propagation and maintenance of a CNS inflammatory response. This review summarizes evidence in support of a case for ischemia and trauma eliciting an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils early after the onset of brain injury and subsequently monocyte infiltration) and mediators (cytokines, chemokines and adhesion molecules). It is clear that de novo up-regulation of pro-inflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain occurs soon following focal ischemia and trauma and at a time when the tissue injury is evolving. The significance of the inflammatory response and its contribution to brain injury are now becoming better understood. Evidence has emerged in support of the role of cytokines in driving the inflammatory response and that this process is causally related to the degree of brain injury. Evidence reviewed includes: (1) the capacity of specific cytokines to exacerbate brain damage; (2) the capacity of specific cytokine blockade to reduce ischemic brain damage; (3) depletion of circulating neutrophils reduces ischemic brain injury, and (4) antagonists of the endothelial-leukocyte adhesion interactions (e.g, anti-ICAM-1) reduce ischemic brain injury. Targeting the cytokines that drive the brain inflammatory response to injury provides opportunities to intervene with novel therapeutics in stroke and neurotrauma.