Role of glial cells in cerebral ischemia

Abstract

Despite intense efforts at the bench and at the bedside, few therapeutic strategies exist to combat the consequences of cerebral ischemia. Traditionally, a "neurocentric" view has dominated research in this field. Evidence is now accumulating that glial cells, in particular astrocytes, play an active and important role in the pathophysiology of cerebral ischemia. Brain energetics, water and ion homeostasis, inflammation, trophic factor production, vascular regulation, neuroneogenesis, and vasculogenesis, among others, are all under the control of glial cells. As a consequence, glial cells have been identified as promising targets for novel therapeutic approaches in brain protection. This review aims at dissecting possible protective as well as destructive roles of astrocytes (and other glial cells) in cerebral ischemia. By emphasizing open issues in this field, we hope to stimulate further research into this relatively unexplored aspect of brain pathophysiology.

P2Y1R-Initiated, IP3R-Dependent Stimulation of Astrocyte Mitochondrial Metabolism Reduces and Partially Reverses Ischemic Neuronal Damage in Mouse

“…5 In general, excitotoxicity and cell death subsequent to disruption of ion homeostasis damages adjacent tissue and expand the infarct by secondary mechanisms. 2 Irrespective of the affected end process, our results suggest that stimulation of astrocyte ATP production is potentially a robust therapeutic strategy to treat brain damage, since it is not inherently dependent on protecting or affecting a single target within neurons.…”

“…They naturally support neuronal survival and modulate neuronal recovery by providing metabolic and trophic support, glutamate and K þ clearance, as well as antioxidant protection during ischemia. 2 In fact, the size of the ischemic infarct appears to be largely determined by the extent of astrocyte death. 2 Consequently, we have targeted astrocytes to enhance neuronal survival and minimize persistent brain damage after stroke.…”

“…2 In fact, the size of the ischemic infarct appears to be largely determined by the extent of astrocyte death. 2 Consequently, we have targeted astrocytes to enhance neuronal survival and minimize persistent brain damage after stroke.…”

“…5 In general, excitotoxicity and cell lysis subsequent to osmotic expansion damage adjacent tissue and expand the infarct by secondary mechanisms. 2,6 Although an ample supply of energy is fundamental to the ability of astrocytes to carry out their neuroprotective functions, it has only recently been demonstrated that astrocyte mitochondria play an important role in energy production. 7,8 Chu et al 9 reported that inhibition of glial mitochondria increases astrocyte swelling and leads to necrotic cell death.…”

Glia: the fulcrum of brain diseases

“…19 Disruption of the blood flow in the brain causes considerable damage and death of neural cells. Reduced oxygen supply (either hypoxia or anoxia) triggers rapid depolarisation of neurones, and greatly compromises their ability to maintain transmembrane ion gradients.…”