Glial Populations in the Human Brain Following Ischemic Injury

Abstract

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, neuronal differentiation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation in the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving poststroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Out of the core: the impact of focal ischemia in regions beyond the penumbra

“…Although glial cells were originally described by Virchow’s and other early studies as purely supportive elements in the brain ( Chvatal and Verkhratsky, 2018 ), years of intensive research revealed their multifaceted function in development and physiological conditions, as well as in various central nervous system (CNS) injuries and diseases, including ischemia ( Verkhratsky, 2007 ; Allen and Lyons, 2018 ; Mihailova et al, 2023 ). Here, we briefly introduce the most well known and most studied glial cell types in ischemia - astrocytes, microglia, oligodendrocytes and NG2-glia.…”

“…In addition to neurons, glial cells are also affected and responsive to ischemic injury ( Mihailova et al, 2023 ). Due to their multiple functions and the large number of released cytokines/chemokines, glial cells often have a “dual face” as they can play an irreplaceable role in mitigating/preventing tissue damage, but they also exacerbate inflammation and excitotoxicity ( Pekny et al, 2014 ; Quincozes-Santos et al, 2021 ).…”