Genetic and Molecular Aspects of Ischemic Stroke

Abstract

Stroke remains a leading cause of disability and death worldwide, with significant public health implications. Ischemic stroke is classified into various subtypes based on etiology, including large-artery atherosclerosis, small-vessel occlusion, and cardioembolism. The middle cerebral artery is often the most affected. The concept of the ischemic core and penumbra is crucial in understanding stroke pathology, where the core suffers irreversible damage, and the penumbra is at high risk if reperfusion is not timely. Genetic predispositions play a significant role in ischemic stroke, with heritability estimates around 37.9%. Monogenic causes account for 1-5% of cases, while polygenic factors are more prevalent. Genome-wide association studies (GWAS) have identified numerous genetic loci associated with ischemic stroke, revealing the complex genetic architecture of the disease. Molecular pathways such as neuroinflammation, excitotoxicity, oxidative stress, apoptosis, and autophagy are involved in the pathophysiology of ischemic stroke. Understanding these pathways offers potential therapeutic targets. This review aims to synthesise recent genetic studies and provide insights into future directions for research and clinical practice in ischemic stroke, emphasising the importance of personalised medicine and targeted therapies.