The Role of Blood-Brain Barrier Transporters in Pathophysiology and Pharmacotherapy of Stroke

Kaushik      Shah; Thomas      Abbruscato

Abstract

Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Since the brain relies on a continuous supply of nutrients and ions via mostly carrier mediated processes across the blood-brain barrier (BBB), any irregularity in these transport mechanisms dramatically affects neuronal function and outcome after acute and chronic stroke. Despite numerous encouraging breakthroughs in preclinical stroke studies that evaluate monotherapies and a prevailing neurocentric approach that has yielded disappointing clinical translation, preclinical stroke studies investigating additional therapeutic targets might be used more effectively in combination with thrombolysis. In this context, this current review discusses the current understanding of dysfunctionional BBB nutrient and ion transport mechanisms involved in stroke pathophsyiology as novel therapeutic approaches. Recognition of the important role of the neurovascular unit in pathophysiology of stroke will provide new opportunities to treat ischemic brain injury, and maintenance of nutrient and ionic homeostasis should facilitate brain repair after stroke.

Keywords: Blood brain barrier, neurovascular unit, stroke, edema, glucose, SGLT, NKCC, NHE, NCX, Phlorizin, insulin.