Oak Ridge Institute for Science and Education Research Participant at the U.S. Environmental Protection Agency/National Center for Environmental Assessment, Office of Research and Development, U.S. EPA, Arlington, VA 22202, USA.
Int J Environ Res Public Health. 2011 Jul;8(7):2980-3018. doi: 10.3390/ijerph8072980. Epub 2011 Jul 20.
Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese and diesel exhaust particles.
小胶质细胞是大脑中的固有细胞，参与调控大脑发育、维持神经内环境稳定、损伤和修复等重要过程。它们属于单核巨噬细胞谱系，作为脑内免疫细胞，调控固有免疫反应；但由于其相对静止的表型和中枢神经系统微环境的严格调控，与其他组织巨噬细胞不同。小胶质细胞主动监测周围实质组织，并对变化做出快速反应，因此任何对神经结构或功能的破坏都可能导致小胶质细胞表型调控的丧失。在许多神经退行性变和神经毒性模型中，突触退变和神经元丢失的早期事件伴随着炎症反应，包括小胶质细胞、血管周围单核细胞的激活和白细胞的募集。在培养物中，小胶质细胞已被证明能够释放几种潜在的细胞毒性物质，如活性氧中间体、一氧化氮、蛋白酶、花生四烯酸衍生物、兴奋性氨基酸和细胞因子；但它们也产生各种神经营养因子，并清除自由基和兴奋毒性物质造成的损伤。作为促炎细胞因子的主要来源，小胶质细胞被认为是神经炎症的关键介质，可以诱导或调节广泛的细胞反应。神经炎症应被视为一个平衡的过程网络，其中细微的改变可以使细胞向不同的结果转变。对于神经炎症和小胶质细胞反应的任何评估，在神经毒性或变性的框架内，确定神经炎症后果的一个关键问题是，该反应是起始事件还是组织损伤的后果。作为文献中环境暴露相关神经炎症的例子，我们对锰和柴油废气颗粒的数据进行了评估。
