Bröer Sonja, Pauletti Alberto
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Front Mol Neurosci. 2024 May 30;17:1404022. doi: 10.3389/fnmol.2024.1404022. eCollection 2024.
Phagocytes maintain homeostasis in a healthy brain. Upon injury, they are essential for repairing damaged tissue, recruiting other immune cells, and releasing cytokines as the first line of defense. However, there seems to be a delicate balance between the beneficial and detrimental effects of their activation in a seizing brain. Blocking the infiltration of peripheral phagocytes (macrophages) or their depletion can partially alleviate epileptic seizures and prevent the death of neurons in experimental models of epilepsy. However, the depletion of resident phagocytes in the brain (microglia) can aggravate disease outcomes. This review describes the role of resident microglia and peripheral infiltrating monocytes in animal models of acutely triggered seizures and epilepsy. Understanding the roles of phagocytes in ictogenesis and the time course of their activation and involvement in epileptogenesis and disease progression can offer us new biomarkers to identify patients at risk of developing epilepsy after a brain insult, as well as provide novel therapeutic targets for treating epilepsy.
吞噬细胞维持健康大脑的体内平衡。在脑损伤时,它们对于修复受损组织、募集其他免疫细胞以及作为第一道防线释放细胞因子至关重要。然而,在癫痫发作的大脑中,它们激活的有益和有害影响之间似乎存在微妙的平衡。在癫痫实验模型中,阻断外周吞噬细胞(巨噬细胞)的浸润或使其耗竭可部分缓解癫痫发作并防止神经元死亡。然而,脑内固有吞噬细胞(小胶质细胞)的耗竭会加重疾病结局。这篇综述描述了脑内固有小胶质细胞和外周浸润单核细胞在急性触发癫痫发作和癫痫动物模型中的作用。了解吞噬细胞在癫痫发生中的作用及其激活的时间进程以及参与癫痫形成和疾病进展的过程,可为我们提供新的生物标志物,以识别脑损伤后有患癫痫风险的患者,并为治疗癫痫提供新的治疗靶点。