Microglial metabolic disturbances and neuroinflammation in cerebral infarction

Cerebral ischemia/reperfusion injury activates microglia, resident immune cells in the brain, and allows the infiltration of circulating immune cells into the ischemic lesions. Microglia play both exacerbating and protective roles in pathological processes and are thus often referred to as double-edged swords. In ischemic brains, blood-borne macrophages play a role that is distinct from that of resident activated microglia. Recently, the metabolic alteration of immune cells in the pathogenesis of inflammatory disorders including cerebral infarction has become a critical target for investigation. We begin this review by describing the multifaceted functions of microglia in cerebral infarction. Next, we focus on the metabolic alterations that occur in microglia during pathological processes. We also discuss morphological changes that take place in the mitochondria, leading to functional disturbances, accompanied by alterations in microglial function. Moreover, we describe the involvement of the reactive oxygen species that are produced during aberrant metabolic activity. Finally, we discuss therapeutic strategies to ameliorate aggravative changes in metabolism. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

Automated summary

Cerebral ischemia/reperfusion injury triggers the activation of microglia and infiltration of circulating immune cells, which contribute to the pathogenesis of cerebral infarction. Metabolic alterations in immune cells, particularly microglia, have emerged as a critical focus for therapeutic strategies in inflammatory disorders. Morphological changes in mitochondria and production of reactive oxygen species also play important roles in exacerbating changes in metabolism.