Barath Abhijeet S, Wu Long-Jun
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA.
J Physiol. 2025 Jun 18. doi: 10.1113/JP288573.
Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non-inflammatory cell death. This process involves a range of well-characterized 'find me' and 'eat me' signals, phagocytic receptors, and less well-characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of developing spontaneous recurrent seizures. Reconciling these dual effects requires a deeper understanding the spatiotemporal dynamics of microglial phagocytosis. The objective of this review is to examine the mechanisms and impact of microglial phagocytosis in the context of epilepsy and to highlight unresolved questions that warrant further investigation in this emerging field.
小胶质细胞是驻留免疫细胞，通过其监测和吞噬功能对维持脑内稳态至关重要。在癫痫发作和癫痫等疾病背景下，小胶质细胞吞噬信号会响应炎症性和非炎症性细胞死亡而被激活。这一过程涉及一系列特征明确的“找到我”和“吃掉我”信号、吞噬受体以及特征不太明确的细胞内信号通路。此外，表观遗传和转录调节因子协调小胶质细胞对癫痫发作的反应，包括吞噬和炎症途径的整合。有趣的是，尽管已证明抑制吞噬作用可改善癫痫发作后的神经元存活和认知表现，但矛盾的是，这会增加发生自发性复发性癫痫的风险。要协调这些双重作用，需要更深入地了解小胶质细胞吞噬作用的时空动态。本综述的目的是研究癫痫背景下小胶质细胞吞噬作用的机制和影响，并突出该新兴领域中有待进一步研究的未解决问题。
