Department of Biology and Biotechnology "Lazzaro Spallanzani", Laboratory of General Physiology, University of Pavia, Pavia, Italy.
Department of Biology and Biotechnology "Lazzaro Spallanzani", Laboratory of General Physiology, University of Pavia, Pavia, Italy.
Vascul Pharmacol. 2022 Aug;145:106997. doi: 10.1016/j.vph.2022.106997. Epub 2022 May 5.
The mechanism whereby an increase in neuronal activity (NA) leads to a local elevation in cerebral blood flow to supply the active neurons with oxygen and nutrients and remove the catabolic waste has been termed neurovascular coupling (NVC). Although it has long been thought that the vasoactive mediators involved in NVC are generated by neurons and astrocytes, recent evidence unveiled the crucial role of cerebrovascular endothelial cells in NVC. Brain capillary endothelial cells express a complement of ion channels, including inward-rectifier K (K2.1) channels, Transient Receptor Potential Ankyrin 1 channels and N-methyl-d-aspartate receptors that enable them to sense NA and thereby initiate the retrograde transmission of both electrical (via endothelium-dependent hyperpolarization) and chemical (via intercellular Ca waves also sustained by TRP Vanilloid 4 channels and inositol-1,4,5-trisphosphate receptors) signals that induce vasodilation in upstream pial arteries and parenchymal arteries. Notably, a defect in the endothelial ion channel machinery (particularly, K2.1 channels) contributes to vascular cognitive impairment and dementia that features many cerebral disorders, including Alzheimer's disease, cerebral small vessel diseases, and traumatic brain injury. Targeting endothelial ion channels through appropriate pharmacological approaches might represent a hitherto unappreciated strategy to rescue CBF and prevent cognitive impairment and dementia in patients affected by cerebral disorders.
神经元活动（NA）增加导致局部脑血流升高，以向活跃神经元提供氧气和营养物质并清除代谢废物的机制被称为神经血管耦合（NVC）。尽管长期以来人们一直认为参与 NVC 的血管活性介质是由神经元和星形胶质细胞产生的，但最近的证据揭示了脑血管内皮细胞在 NVC 中的关键作用。脑毛细血管内皮细胞表达一系列离子通道，包括内向整流钾（K2.1）通道、瞬时受体电位锚蛋白 1 通道和 N-甲基-D-天冬氨酸受体，使它们能够感知 NA，从而启动电信号（通过内皮细胞依赖性去极化）和化学信号（通过细胞间 Ca 波传递，也由瞬时受体电位香草酸 4 通道和肌醇 1,4,5-三磷酸受体维持）的逆行传递，从而导致上游软脑膜动脉和实质动脉的血管扩张。值得注意的是，内皮离子通道机制（特别是 K2.1 通道）的缺陷导致血管性认知障碍和痴呆，这是许多脑疾病的特征，包括阿尔茨海默病、脑小血管疾病和创伤性脑损伤。通过适当的药理学方法靶向内皮离子通道可能代表一种迄今为止尚未被认识的策略，可以挽救 CBF 并预防受脑疾病影响的患者的认知障碍和痴呆。
