MacVicar Brian A, Newman Eric A
Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455.
Cold Spring Harb Perspect Biol. 2015 Mar 27;7(5):a020388. doi: 10.1101/cshperspect.a020388.
Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from active neurons evoke Ca(2+) increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K(+) from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca(2+) signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow.
神经元活动导致大脑血流量增加，这种反应被称为功能性充血。星形胶质细胞在介导这种反应中起重要作用。活跃神经元释放的神经递质会引起星形胶质细胞内钙离子增加，导致星形胶质细胞终足将花生四烯酸的血管活性代谢产物释放到血管上。前列腺素E2（PGE2）和环氧二十碳三烯酸（EETs）的合成会使血管扩张，而20-羟基二十碳四烯酸（20-HETE）会使血管收缩。星形胶质细胞终足释放钾离子也可能有助于血管舒张。氧气调节星形胶质细胞对血流的调节。在常氧条件下，星形胶质细胞的钙离子信号传导会导致血管舒张，而在高氧条件下，则有利于血管收缩。星形胶质细胞也有助于血管张力的产生。星形胶质细胞持续释放20-HETE和ATP会使血管平滑肌细胞收缩，产生血管张力。在包括阿尔茨海默病和糖尿病视网膜病变在内的病理条件下，正常星形胶质细胞生理功能的破坏会损害对血流的调节。
