Neurovascular protection by peroxisome proliferator-activated receptor α in ischemic stroke

Ischemic stroke is a leading cause of death and disability worldwide. Currently, the only pharmacological therapy for ischemic stroke is thrombolysis with tissue plasminogen activator that has a narrow therapeutic window and increases the risk of intracerebral hemorrhage. New pharmacological treatments for ischemic stroke are desperately needed, but no neuroprotective drugs have successfully made it through clinical trials. Beneficial effects of peroxisome proliferator-activated receptor alpha (PPAR alpha) activation on vascular integrity and function have been reported, and PPAR alpha agonists have clinically been used for many years to manage cardiovascular disease. Thus, PPAR alpha has gained interest in recent years as a target for neurovascular disease such as ischemic stroke. Accumulating preclinical evidence suggests that PPAR alpha activation modulates several pathophysiological hallmarks of stroke such as oxidative stress, blood-brain barrier (BBB) dysfunction, and neuroinflammation to improve functional recovery. Therefore, this review summarizes the various actions PPAR alpha exerts in neurovascular health and disease and the potential of employing exogenous PPAR alpha agonists for future pharmacological treatment of ischemic stroke.