Microglial metabolic disturbances and neuroinflammation in cerebral infarction

J Pharmacol Sci. 2021 Jan;145(1):130-139. doi: 10.1016/j.jphs.2020.11.007. Epub 2020 Nov 21.

Abstract

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.

Keywords: Glycolysis; Macrophage; Nrf2; OXPHOS; ROS.

Publication types

  • Review

MeSH terms

  • Cerebral Infarction / immunology
  • Cerebral Infarction / metabolism*
  • Cerebral Infarction / pathology*
  • Cerebral Infarction / therapy
  • Glycolysis
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Macrophages
  • Microglia / immunology
  • Microglia / metabolism*
  • Microglia / pathology*
  • Mitochondria / pathology
  • NF-E2-Related Factor 2 / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species