BREAKING BARRIERS: THE VITAL ROLE OF THE BLOOD-BRAIN BARRIER IN ISCHEMIC STROKE PATHOLOGY AND THE DEVELOPMENT OF NOVEL THERAPEUTIC APPROACHES

Abstract

Ischemic stroke is a common and debilitating disease characterized by the obstruction of blood flow to the brain, leading to tissue damage and neurological deficits. Despite significant advances in stroke management, current treatments are still inadequate, and the development of novel therapies is urgently needed. While the collaborative effort to discover neuroprotective agents to promote optimal recovery post-stroke has been massive, there has been no advancement of novel drugs beyond Phase III clinical trials. Recent studies suggest that targeting the blood-brain barrier (BBB) may offer a promising approach to stroke treatment that had been previously overlooked. The BBB is a highly selective membrane that separates the brain from the circulating blood, regulating the entry of molecules and cells into the brain. Dysfunction of the BBB is a hallmark of ischemic stroke, as it leads to an influx of harmful substances into the brain, exacerbating tissue damage and inflammation. This review discusses the various known mechanisms involved in the breakdown of the BBB, identified potential targets for neuroprotection, and the experimental models that have demonstrated and continue to demonstrate progress in this field. The Ronaldson Lab at the University of Arizona has been a major contributor to BBB research and the progression of ischemic stroke therapeutic investigation.