Examining the Impact of Microglia on Ischemic Stroke With an Emphasis on the Metabolism of Immune Cells

Abstract

Background: Ischemic stroke, a major cause of disability and the second leading cause of death, poses a significant public health challenge. Post-stroke inflammation can harm the blood-brain barrier and worsen neurological deficits, which are key factors in neuronal damage in patients with ischemic stroke. Microglia are crucial in the central nervous system, involved in inflammation, neuronal damage, and repair after cerebral ischemia. While cellular immune metabolism has been widely studied, its role in ischamic stroke remains unclear.

Aim: This review aims to examine how inflammation affects the phenotypic characteristics of immune cells after ischemic stroke and to explore the effects of the immune metabolic microenvironment on the phenotypic profiles and functions of microglia in ischemic stroke.

Method: The review refers to the available literature in PubMed, searching for critical terms related to Ischemic stroke, neuroinflammation, microglia, and immunometabolism.

Result: In this review, we found that during stroke progression, microglia can dynamically switch between pro-inflammatory and anti-inflammatory phenotypes. Microglial glycometabolism includes oxidative phosphorylation and glycolysis, and lipid metabolism involves lipid synthesis and breakdown. Modulating the production of inflammatory mediator precursors can induce an anti-inflammatory phenotype in microglia.

Conclusion: Thus, studying microglial metabolic pathways and their products may offer new insights for ischemic stroke treatment.

Keywords: immunometabolism; ischemic stroke; microglia; neuroinflammation.

FIGURE 1

Schematic diagram of anti‐inflammatory phenotype polarization of microglia. (By Figdraw).

FIGURE 2

Metabolic Reprogramming of Microglia. (By Figdraw). (A) In a healthy brain, microglial cells exhibit metabolic flexibility, preferentially metabolizing glucose. Glutamine metabolism via glutaminolysis supports the energy demands of microglial cells. The utilization of fatty acids for ATP production remains controversial. (B) Following ischemic stroke, metabolic reprogramming occurs in microglial cells. Stimulated by various inflammatory signals, microglia reprogram their intracellular metabolic pathways. Reprogramming is characterized by increased glycolytic flux, accumulation of certain TCA metabolites, decreased mitochondrial respiration, and increased transcriptional control of HIF‐1α and mTOR. CCR4, C‐C Chemokine Receptor Type 4; CKLF1, Chemokine‐like factor 1, FA, fatty acid; GLUTs, Glucose transporters; HIF‐1α, hypoxia inducible factor‐1α; HK, hexokinase; IFN‐γ, interferon‐γ; IGF1, Insulin‐like Growth Factor 1; IL‐1β, interleukin‐1β; mTOR, mammalian target of rapamycin; OXPHOS, oxidative phosphorylation; PFKFB3, 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3; TCA, tricarboxylic acid.