Metabolic reprogramming of microglia and astrocytes is a regulatory factor of neuroinflammation in ischemic stroke

Ischemic stroke is one of the most common diseases worldwide, with a high incidence and mortality rate. In the pathological process of ischemia of nervous tissue, neuroinflammation is an important factor that determines the functional prognosis of the outcome of the disease. During the formation of an ischemic focus, microglial cells and astrocytes are activated, which leads to the launch of a cascade of neuroinflammatory reactions that play an important role in the pathophysiology of ischemic stroke. Activated microglial cells and astrocytes are able to form a variety of phenotypes depending on the corresponding parameters of the microenvironment. These phenotypes can have both neurotoxic and neuroprotective effects. On the one hand, when nerve tissue is damaged, glial cells contribute to the removal of cellular debris, maintain ionic homeostasis, regulate the extracellular content of neurotransmitters and ensure the trophism of neurons. On the other hand, microglia and astrocytes can acquire a pro-inflammatory phenotype characterized by the secretion of inflammatory cytokines, which contributes to the progression of neuroinflammation and tissue damage. Thus, astrocytes and microglia undergo both morphological and functional rearrangements, thereby actively participating in neuroinflammation due to the release of pro-inflammatory or anti-inflammatory factors. It is important to note that these rearrangements are associated with metabolic reprogramming, which leads to a change in the activity of metabolic pathways to compensate for the lack of energy and building materials caused by impaired cerebral blood flow. The pro-inflammatory phenotype of microglia is characterized by activation of glycolysis, the pentose phosphate pathway, synthesis of fatty acids and glutamine, whereas the anti-inflammatory phenotype demonstrates increased oxidative phosphorylation and oxidation of fatty acids. Reactive astrocytes are characterized by increased glycolysis, glycogenolysis and reduced glutamate uptake. Recently, there has been increasing evidence that manipulation of glial cell homeostasis can be used to switch from a neurotoxic phenotype to a neuroprotective one. A comprehensive understanding of the basic mechanisms of switching metabolic phenotypes can potentially allow targeted reprogramming of glial cells during the pathological process, which can be used in therapeutic approaches for the treatment of the consequences of ischemic stroke. This review presents current ideas about metabolic reprogramming in astrocytes and microglial cells in the context of pathophysiological processes in cerebral ischemia.

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