New roles of reactive astrocytes in the brain; an organizer of cerebral ischemia

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The brain consists of neurons and much higher number of glial cells. They communicate each other, by which they control brain functions. The brain is highly vulnerable to several insults such as ischemia, but has a self-protective and self-repairing mechanisms against these. Ischemic tolerance or preconditioning is an endogenous neuroprotective phenomenon, where a mild non-lethal ischemic episode can induce resistance to a subsequent severe ischemic injury in the brain. Because of its neuroprotective effects against cerebral ischemia or stroke, ischemic tolerance has been widely studied. However, almost all studies have been performed from the viewpoint of neurons. Glial cells are structurally in close association with synapses. Recent studies have uncovered the active roles of astrocytes in modulating synaptic connectivity, such as synapse formation, elimination and maturation, during development or pathology. However, glia-mediated ischemic tolerance and/or neuronal repairing have received only limited attention. We and others have demonstrated that glial cells, especially astrocytes, play a pivotal role in regulation of induction of ischemic tolerance as well as repairing/remodeling of neuronal networks by phagocytosis. Here, we review our current understanding of (1) glial-mediated ischemic tolerance and (2) glia-mediated repairing/remodeling of the penumbra neuronal networks, and highlight their mechanisms as well as their potential benefits, problems, and therapeutic application.HighlightsReactive astrocytes after brief cerebral ischemia control both ischemic tolerance and phagocytosis.Ischemic tolerance was dependent on activation of astrocytes, and subsequent induction of HIF-1α in astrocytes.Unlike neurons, astrocytic HIF-1α was not dependent on hypoxia but dependent on upregulation/activation of P2X7 receptors.Reactive astrocytes also have essential roles in repairing/remodeling of the penumbra neuronal network by phagocytosis.

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