Neurovascular Unit as a target of regenerative therapy

Abstract

Endothelial damage following plaque rupture triggers platelet thrombosis. Therefore in the acute phase of atherosclerosis, strong dual antiplatelet therapy (DAPT) is effective in suppression of further thrombosis. In addition, novel therapeutic approaches targeting on the damaged endothelium is under development, which include acceleration of re-endothelialization on the ruptured plaque, promotion of endothelial cell division/migration, tightening endothelial cell junction, reinforcing endothelial attachment to the underlying connective tissue, and replacing adhered platelets with endothelial cells. In addition, we developed tissue engineered blood vessel system in a membrane, which can effectively induce meningeal collateral flow and save ischemic lesion in the territory of major artery stenosis. We reported the validity of this method in mouse using MCA permanent occlusion model. In this membrane structure, vessel endothelial cells and supporting cells would develop tissue engineered vessels and create anastomosis with meningeal vessels. Among constituents of neurovascular unit, pericyte might play the most pivotal role in the regenerative therapy after ischemic event. We now propose “proximal integration model” as a mechanism to control capillary flow after neural activation. Since capillary does not have constriction apparatus, precapillary arteriole may regulate capillary flow. Instead of constricting by itself, pericyte may transduce information of neural activation proximally.