Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain.
Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain.
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周细胞变性导致神经血管解偶联并限制大脑的供氧
DOI：
10.1038/nn.4489
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发表时间：
2017-03
影响因子：
25
通讯作者：
Zlokovic BV
中科院分区：
文献类型：
--
作者：
Kisler K;Nelson AR;Rege SV;Ramanathan A;Wang Y;Ahuja A;Lazic D;Tsai PS;Zhao Z;Zhou Y;Boas DA;Sakadžić S;Zlokovic BV
周细胞是脑毛细血管周围的壁细胞。它们位于内皮细胞、星形胶质细胞和神经元之间的神经血管单位的中央。这个位置允许它们调节大脑的关键神经血管功能。然而，周细胞在调节脑血流（CBF）和神经血管耦联中的作用仍存在争议。使用功能丧失的周细胞缺陷小鼠，在这里，我们表明，周细胞变性减少全球和个人的毛细血管CBF神经元刺激的反应，导致神经血管解偶联，减少氧气供应到大脑和代谢应激。随着时间的推移，神经血管缺陷导致神经元兴奋性受损和神经退行性变化。因此，在神经系统疾病如阿尔茨海默病中看到的周细胞变性可能导致与人类疾病相关的神经血管功能障碍和神经变性。
Pericytes are perivascular mural cells of brain capillaries. They are positioned centrally in the neurovascular unit between endothelial cells, astrocytes and neurons. This position allows them to regulate key neurovascular functions of the brain. The role of pericytes in the regulation of cerebral blood flow (CBF) and neurovascular coupling remains, however, under debate. Using loss-of-function pericyte-deficient mice, here we show that pericyte degeneration diminishes global and individual capillary CBF responses to neuronal stimuli, resulting in neurovascular uncoupling, reduced oxygen supply to the brain and metabolic stress. Neurovascular deficits lead over time to impaired neuronal excitability and neurodegenerative changes. Thus, pericyte degeneration as seen in neurological disorders such as Alzheimer's disease may contribute to neurovascular dysfunction and neurodegeneration associated with human disease.