Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones

Abstract

The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital to the successful development of clinically useful medications. Stroke is generally accepted as the leading cause of adult disability globally and ischemic stroke accounts for the most common form of the two main stroke types. Despite its health and socioeconomic burden, there is still minimal availability of effective pharmacological therapies for its treatment. In this review, we take an in-depth look at the etiology and pathophysiology of ischemic stroke, including molecular and cellular changes. This is followed by a highlight of drugs, cellular therapies, and complementary medicines that are approved or undergoing clinical trials for the treatment and management of ischemic stroke. We also identify unexplored potential targets in stroke pathogenesis that can be exploited to increase the pool of effective anti-stroke and neuroprotective agents through de novo drug development and drug repurposing.

Comprehensive Management of Stroke: From Mechanisms to Therapeutic Approaches

“…Cerebral ischemic damage also activates the extrinsic pathway, which can be activated independently or simultaneously to the intrinsic pathway mechanisms. It can be mediated through the activation of neuronal membrane receptors, such as TRAIL-R and FasL, leading to an overexpression of caspase-8 and caspase-3, thereby activating apoptotic signalling [23] 2.6. Other Mechanisms of Regulated Cell Death Oxidative stress and increased intracellular calcium levels induce permanent neuronal damage, which induces expression of phosphatidylserine (PS) on the membrane cell.…”

“…Intravenous thrombolysis (IVT) with a tissue-type plasminogen activator (tPA) named alteplase has been the only and preferred treatment for 25 years; it is currently the only FDA and EU approved medical treatment for patients with acute ischemic stroke (AIS) [23].…”