Role of microglia in stroke.

Autor: Planas AM; Cerebrovascular Research Laboratory, Department of Neuroscience and Experimental Therapeutics, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Cerebrovascular Diseases, Area of Clinical and Experimental Neuroscience, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Jun; Vol. 72 (6), pp. 1016-1053. Date of Electronic Publication: 2024 Jan 04.
DOI: 10.1002/glia.24501
Abstrakt: Microglia play key roles in the post-ischemic inflammatory response and damaged tissue removal reacting rapidly to the disturbances caused by ischemia and working to restore the lost homeostasis. However, the modified environment, encompassing ionic imbalances, disruption of crucial neuron-microglia interactions, spreading depolarization, and generation of danger signals from necrotic neurons, induce morphological and phenotypic shifts in microglia. This leads them to adopt a proinflammatory profile and heighten their phagocytic activity. From day three post-ischemia, macrophages infiltrate the necrotic core while microglia amass at the periphery. Further, inflammation prompts a metabolic shift favoring glycolysis, the pentose-phosphate shunt, and lipid synthesis. These shifts, combined with phagocytic lipid intake, drive lipid droplet biogenesis, fuel anabolism, and enable microglia proliferation. Proliferating microglia release trophic factors contributing to protection and repair. However, some microglia accumulate lipids persistently and transform into dysfunctional and potentially harmful foam cells. Studies also showed microglia that either display impaired apoptotic cell clearance, or eliminate synapses, viable neurons, or endothelial cells. Yet, it will be essential to elucidate the viability of engulfed cells, the features of the local environment, the extent of tissue damage, and the temporal sequence. Ischemia provides a rich variety of region- and injury-dependent stimuli for microglia, evolving with time and generating distinct microglia phenotypes including those exhibiting proinflammatory or dysfunctional traits and others showing pro-repair features. Accurate profiling of microglia phenotypes, alongside with a more precise understanding of the associated post-ischemic tissue conditions, is a necessary step to serve as the potential foundation for focused interventions in human stroke.
(© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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