Department of Neuropathology, University Medical Centre Göttingen Göttingen, Germany ; Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende Göttingen, Germany.
Department of Neuropathology, University Medical Centre Göttingen Göttingen, Germany.
Front Cell Neurosci. 2014 May 22;8:138. doi: 10.3389/fncel.2014.00138. eCollection 2014.
In healthy individuals, infections of the central nervous system (CNS) are comparatively rare. Based on the ability of microglial cells to phagocytose and kill pathogens and on clinical findings in immunocompromised patients with CNS infections, we hypothesize that an intact microglial function is crucial to protect the brain from infections. Phagocytosis of pathogens by microglial cells can be stimulated by agonists of receptors of the innate immune system. Enhancing this pathway to increase the resistance of the brain to infections entails the risk of inducing collateral damage to the nervous tissue. The diversity of microglial cells opens avenue to selectively stimulate sub-populations responsible for the defence against pathogens without stimulating sub-populations which are responsible for collateral damage to the nervous tissue. Palmitoylethanolamide (PEA), an endogenous lipid, increased phagocytosis of bacteria by microglial cells in vitro without a measurable proinflammatory effect. It was tested clinically apparently without severe side effects. Glatiramer acetate increased phagocytosis of latex beads by microglia and monocytes, and dimethyl fumarate enhanced elimination of human immunodeficiency virus from infected macrophages without inducing a release of proinflammatory compounds. Therefore, the discovery of compounds which stimulate the elimination of pathogens without collateral damage of neuronal structures appears an achievable goal. PEA and, with limitations, glatiramer acetate and dimethyl fumarate appear promising candidates.
在健康个体中，中枢神经系统（CNS）感染相对较少。基于小胶质细胞吞噬和杀死病原体的能力，以及免疫功能低下的 CNS 感染患者的临床发现，我们假设完整的小胶质细胞功能对于保护大脑免受感染至关重要。小胶质细胞对病原体的吞噬作用可以通过先天免疫系统受体的激动剂来刺激。增强这一途径以增加大脑对感染的抵抗力，可能会导致对神经组织的附带损伤。小胶质细胞的多样性为选择性刺激负责抵御病原体的亚群提供了途径，而不会刺激负责对神经组织造成附带损伤的亚群。棕榈酸乙醇酰胺（PEA）是一种内源性脂质，可增加体外小胶质细胞对细菌的吞噬作用，而无明显的促炎作用。它在临床上的测试显然没有严重的副作用。醋酸格拉替雷可增加小胶质细胞和单核细胞对乳胶珠的吞噬作用，二甲基富马酸可增强感染巨噬细胞中人类免疫缺陷病毒的清除，而不会诱导促炎化合物的释放。因此，发现刺激病原体消除而不引起神经元结构附带损伤的化合物似乎是一个可行的目标。PEA 以及有一定限制的醋酸格拉替雷和二甲基富马酸似乎是有前途的候选药物。
