Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.
Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.
复制标题
毛细血管退化通过诱导上游移行血管收缩而导致持续的局部灌注不足。
DOI：
10.1101/2023.10.28.564529
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Shih,AndyY
中科院分区：
文献类型：
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作者：
Bonney,StephanieK;Nielson,CaraD;Sosa,MariaJ;Shih,AndyY
在大脑中，微血管感觉网协调氧气输送到神经元活动区域。这涉及到密集的毛细血管网络，将传导信号向上游发送到供给小动脉，以促进血管舒张和血液流动。尽管这一过程对于健康脑组织的代谢供应至关重要，但它也可能是疾病的一个脆弱点。毛细血管网络的恶化是许多神经系统疾病和损伤的一个特征，而毛细血管网络在血管损伤期间如何参与仍不清楚。我们对年轻成年壁细胞报告小鼠进行体内双光子显微镜检查，并使用单毛细血管的精确双光子激光照射诱导局灶性毛细血管损伤。我们发现，约 59% 的损伤导致损伤后 7 至 14 天毛细血管段退化，其余部分在 7 天内修复并重新建立血流。导致毛细血管消退的损伤在清醒小鼠和麻醉小鼠中至少在损伤后 21 天诱导上游小动脉-毛细血管过渡区 (ACT) 持续血管收缩。 ACT 区的血管舒缩动力学程度长期减弱，从而减少了 ACT 区和继发性、未受伤的下游毛细血管的血流量。这些发现表明局灶性毛细血管损伤和退化如何损害微血管感觉网并导致脑灌注不足。
In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion.