Division of Neurology, Duke University Medical Center, Durham, 27710 NC, USA.
J Neuroimmune Pharmacol. 2009 Dec;4(4):399-418. doi: 10.1007/s11481-009-9164-4. Epub 2009 Aug 5.
The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain's innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed.
大脑中的免疫反应已经得到了广泛的研究，虽然许多研究都集中在促炎细胞毒性反应上，但大脑的先天免疫系统表现出显著的异质性。小胶质细胞与其他组织巨噬细胞一样，在感染或损伤后参与修复和解决过程，以恢复正常的组织稳态。这篇综述检查了导致自我毒性降低以及修复和重塑大脑受损细胞外基质的机制。解决过程的一部分涉及到将巨噬细胞功能激活转变为包括减少促炎介质、增加抗炎细胞因子的产生和释放以及产生参与修复和重建受损大脑的细胞活性因子。已经确定了两种部分重叠和互补的功能巨噬细胞状态，并将其称为替代性激活和获得性失活。讨论了这两种状态的免疫抑制和修复过程，以及替代性激活和获得性失活如何参与大脑中的慢性神经炎症。
