Kahn M A, Ellison J A, Speight G J, de Vellis J
Department of Anatomy and Cell Biology, UCLA, School of Medicine, USA.
Brain Res. 1995 Jul 10;685(1-2):55-67. doi: 10.1016/0006-8993(95)00411-i.
In response to physical or chemical brain injury, the mammalian central nervous system (CNS) often reacts by evoking astrogliosis. The most prominent feature describing this state is an upregulation of glial fibrillary acidic protein (GFAP). The agent(s) responsible for inducing astrogliosis remains unclear; however, recent observations have shown cytokines may play a pivotal role. During CNS trauma, macrophages and lymphocytes infiltrate the CNS where they are thought to synthesize and secrete cytokines; moreover, activated microglia and reactive astrocytes are known to be capable of cytokine production. We are the first to report that an intracerebral injection of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), increases astrogliosis and the appearance of activated microglia in the neonatal rat. This response to CNTF was comparable to the response observed in animals receiving a well known pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Only a moderate increase was observed in the proliferative index of cytokine-injected animals; therefore, we conclude that GFAP is largely upregulated in a pre-existing GFAP negative cell population. Interestingly, coinjections of CNTF and TNF-alpha appeared to act synergistically. Coinjected animals displayed a wave of hypertrophied astrocytes reaching far into the contralateral hemisphere. No contralateral spreading of microglia was observed. This article clearly provides interesting information regarding the regulatory mechanisms that govern astrogliosis and discusses the probable relationship of reactive astrocytes to microglia.
针对物理性或化学性脑损伤，哺乳动物中枢神经系统（CNS）常通过引发星形胶质细胞增生做出反应。描述这种状态的最显著特征是胶质纤维酸性蛋白（GFAP）上调。引发星形胶质细胞增生的因素尚不清楚；然而，最近的观察表明细胞因子可能起关键作用。在中枢神经系统创伤期间，巨噬细胞和淋巴细胞浸润中枢神经系统，据认为它们在其中合成和分泌细胞因子；此外，已知活化的小胶质细胞和反应性星形胶质细胞能够产生细胞因子。我们首次报道，向新生大鼠脑内注射多效性细胞因子睫状神经营养因子（CNTF）会增加星形胶质细胞增生和活化小胶质细胞的出现。对CNTF的这种反应与在接受众所周知的促炎细胞因子肿瘤坏死因子-α（TNF-α）的动物中观察到的反应相当。在注射细胞因子的动物的增殖指数中仅观察到适度增加；因此，我们得出结论，GFAP在预先存在的GFAP阴性细胞群体中大量上调。有趣的是，CNTF和TNF-α的联合注射似乎具有协同作用。联合注射的动物显示出一波肥大的星形胶质细胞延伸到对侧半球深处。未观察到小胶质细胞向对侧扩散。本文清楚地提供了有关控制星形胶质细胞增生的调节机制的有趣信息，并讨论了反应性星形胶质细胞与小胶质细胞之间可能的关系。
