Cellular Indicators Of Neuronal Insult

脑中炎性细胞的局部激活可能导致急性脑损伤后发生的神经元死亡以及更渐进的退行性过程。在这个网络中，各种细胞沟通和调节免疫和炎症反应的启动，传播和抑制的复杂过程。通过常驻免疫细胞网络和神经元与神经胶质之间的细胞-细胞相互作用，在损伤时发生级联反应，其发出可能导致神经元死亡的信号事件。这个项目的目的是确定神经胶质反应的关键特征，这些特征可能导致或加剧正在进行的神经元死亡过程。这些特征不仅包括单个细胞应答，还包括可能影响这些应答结果的细胞外环境。我们已经确定，大脑中的炎症反应与外周中的炎症反应大致相同。作为宿主的防御反应，它可以保护大脑，然而，当反应变得失调时，这可能导致不良事件。在这个框架下，我们已经报道了小胶质细胞不仅在损伤反应的初始阶段而且在损伤后的修复过程中都是至关重要的。在此过程中，肿瘤坏死因子的上调和小胶质细胞通过细胞周期过程的调节似乎是关键因素。在有机金属三甲基锡诱导的神经元死亡的活跃过程中，我们发现了大量新神经元的产生。修复的水平是实质性的，并且发生在高炎症信号的环境中。通过这个网络，各种细胞沟通和调节免疫和炎症反应的启动，传播和抑制的复杂过程。在过去的一年中，我们继续我们的研究，使用这种化学诱导的海马神经元损伤模型，并确定了分子信号发生之前的证据，神经元的侮辱，除了识别的形态和细胞反应，发生在小胶质细胞的早期。这些研究支持“炎症”在为神经元修复提供刺激环境中的积极作用，并且我们计划使用cDNA微阵列分析和其他技术在基因表达水平上继续我们对该模型的检查，如细胞免疫组织化学技术，以定位负责修复和再生的细胞。这些研究提供了确定关键信号条件的承诺，以增强内源性神经发生，这可能适用于急性损伤，如中风，头部创伤和治疗方法，更渐进的神经退行性疾病。

Local activation of inflammatory cells in the brain may contribute to neuronal death that occurs following acute brain injury as well as more progressive degenerative processes. In this network, various cells communicate and regulate complex processes of initiation, propagation, and suppression of immune and inflammatory responses. Through the resident immune cell network and the cell-cell interactions between the neurons and the glia a cascade of responses occur upon insult that signal events that may lead to neuronal death. The purpose of this project is to identify the critical features of the glia response that may either cause or exacerbate an ongoing process of neuronal death. These features include not only the individual cell response but also the extracellular environment that may influence the outcome of such responses. We have determined that the inflammatory response in the brain serves much the same was as that in the periphery. As a host defense response it serves to protect the brain however, when the response becomes dysregulated this can lead to adverse events. Under this framework we have reported that microglia cells are critical not only in the initial phase of the damage response but also in the repair process following injury. During this process both the up-regulation of tumor necrosis factor and the regulation of microglia cells via cell cycle processes appear to be critical factors . In the active process of neuronal death induced by the organo-metal, trimethyltin, we characterized a dramatic generation of new neurons for replacement. The level of repair is substantial and occurs within an environment of high inflammatory signals. Through this network, various cells communicate and regulate complex processes of initiation, propagation, and suppression of immune and inflammatory responses. Over the past year we have continued our studies using this chemical-induced model of hippocampal neuronal damage and have characterized the molecular signals that occur prior to evidence of neuronal insult in addition to identifying the morphological and cellular responses that occur early in the microglia. These studies support a positive role for "inflammation" in providing a stimulating environment for neuronal repair and we plan to continue our examination of this model at the gene expression level using cDNA microarray analysis and other techniques as cell as immmunohistochemical techniques to localize the cells responsible for repair and regeneration. Such studies offer the promise of identifying the critical signal conditions to enhance endogenous neurogenesis which may be applicable to acute injuries such as stroke, head trauma and therapeutic approaches for more progressive neurodegenerative disorders.