Remodeling the brain after stroke by astrocytic phagocytosis

[Speaker] Yosuke Morizawa:1
[Co-author] Schuichi Koizumi:2
1:Super-network Brain Physiology, Tohoku University, Japan, 2:Dept. Neuropharmacology, Univ. Yamanashi, Japan

Remodeling the brain by clearance of unnecessary network and debris is thought to be essential for the maintenance of brain function and microenvironment. Such events include phagocytosis, which is thought to be limited to the professional phagocytes, i.e., microglia in the brain.
Here, we show that astrocytes, other type of glia, also show highly phagocytic phenotype after stroke with different spatiotemporal patterns of microglia. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia.
Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to recovery or remodeling of damaged tissues and penumbra networks.
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