近日，美国霍华德休斯医学院教授顾成华及其研究小组揭示了脑内皮缝隙连接耦合使神经血管耦合过程中的血管扩张快速传播。相关论文于2025年7月16日发表在《细胞》杂志上。

小组证明，内皮间隙连接耦合使血管舒张信号在神经血管耦合期间通过血管系统的远程传播。这些间隙连接的分子组成沿着动脉-静脉轴划分，动脉是耦合最强烈的部分。在清醒小鼠中使用光遗传学和视觉刺激，该团队发现急性，动脉内皮细胞类型特异性的Cx37和Cx40缺失会消除动脉间隙连接偶联并导致血管舒张受损。具体来说，小组证明了动脉内皮间隙连接耦合决定了神经活动引发的血管舒张传播的速度和空间范围。这些发现表明，内皮缝隙连接作为神经血管耦合的信号通路，使有限的能量资源能够灵活有效地分配。

据了解，为了满足大脑时时刻刻的能量需求，神经活动会迅速增加局部血流量。这个过程被称为神经血管耦合，涉及大脑动脉网络快速、协调的血管扩张。

附：英文原文

Title: Brain endothelial gap junction coupling enables rapid vasodilation propagation during neurovascular coupling

Author: Trevor Krolak, Luke Kaplan, Kathleen Navas, Lujing Chen, Austin Birmingham, Daniel Ryvkin, Victoria Izsa, Megan Powell, Zhuhao Wu, Benjamin E. Deverman, Chenghua Gu

Issue&Volume: 2025-07-16

Abstract: To meet the brain’s moment-to-moment energy demand, neural activation rapidly increases local blood flow. This process, known as neurovascular coupling, involves rapid, coordinated vasodilation of the brain’s arterial network. Here, we demonstrate that endothelial gap junction coupling enables long-range propagation of vasodilation signals through the vasculature during neurovascular coupling. The molecular composition of these gap junctions is zonated along the arterio-venous axis, with arteries being the most strongly coupled segment. Using optogenetics and visual stimuli in awake mice, we found that acute, arterial endothelial cell type-specific deletion of Cx37 and Cx40 abolishes arterial gap junction coupling and results in impaired vasodilation. Specifically, we demonstrated that arterial endothelial gap junction coupling determines both the speed and the spatial extent of vasodilation propagation elicited by neural activity. These findings indicate that endothelial gap junctions serve as a signaling highway for neurovascular coupling, enabling flexible and efficient distribution of limited energetic resources.

DOI: 10.1016/j.cell.2025.06.030

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00732-9