Endothelial energy failure as a therapeutic target in elderly strokes

Despite the fact that a third of stroke patients are over the age of 80, specialized stroke management in the elderly is in its infancy. The signature poor blood flow in the aged brain has been shown to synchronize with impaired neurovascular coupling and inflammation in the course of acute occlusive stroke. The striking pre-clinical findings indicate endothelial energy failure precedes cerebrovascular aging and may bridge the aging phenotype of cerebral blood flow to cerebrovascular dysfunction in the elderly. As the gatekeeper for energy supply and shuttling to different brain resident cells, the endothelial energy machinery affects a wide range of cerebral activities. The review focuses on the existing evidence linking endothelial energy failure with the detrimental events in the acute phase of ischemic stroke, including collateral failure, excitotoxicity, and fluid retention. This simplified picture aims to highlight the knowledge gaps and potential targets to correct the bioenergetic imbalance in the elderly stroke. The recent clinical studies demonstrating promising effects of mitotherapy in old stroke patients further signify the correction of energy machinery cerebral vessels, encouraging meticulous characterization of the old endothelium and bioengineering approaches for specialized drug delivery.