Ischemic Stroke: Pathophysiology and Evolving Treatment Approaches

Abstract

Stroke remains a leading cause of mortality and disability, with ischemic stroke being the most common type. It occurs due to reduced cerebral blood flow, leading to a cascade of events initiated by oxygen and nutrient deprivation, triggering excitotoxicity, oxidative stress, and inflammation and finally culminating in neuronal injury and death. Key molecular players in ischemic stroke include glutamate receptors, acid-sensing ion channels, and purinergic receptors, exacerbating cellular damage through calcium influx, oxidative stress, and mitochondrial dysfunction. Understanding these mechanisms has shaped therapeutic strategies, such as neuroprotective agents and stem cell therapies. Current treatments such as tissue plasminogen activator (tPA) emphasize timely intervention, yet challenges persist in patient-specific variability and accessibility. This review provides an overview of ischemic stroke pathophysiology, emphasizing cellular responses to ischemia and current and future therapeutic approaches including stem cell therapies aimed at mitigating stroke-induced disabilities and improving long-term outcomes.

Keywords: ASIC; Ischemic stroke; NMDA; ion channels; stroke therapy.

Figure 1.

Schematic representation of the biological events in ischemic stroke. The figure explains the events happening during an ischemic stroke finally culminating in cellular death (apoptosis or necrosis).

Figure 2.

The three different types of stroke treatment strategies. The figure explains the patient care and the different types of therapeutic strategies received after the onset of the disease.

Figure 3.

Cavity-detection guided Blind Docking study of GABA receptor agonist (diazepam) and GABA receptor molecule. The GABA structure (pdb format) is selected and docked blindly with Diazepam known structure and then with the CB-dock software were analyzed together. The final image represents the drug (ball and stick structure, yellow) nicely binding with the GABA receptor. The Vina score of the interaction is −6.7 which represents the most favorable binding affinity between the drug diazepam and 2 chains of the GABA molecule.

Figure 4.

Cavity-detection guided Blind Docking study of TLR4 ligand Isoquercetin and TIR domain of Toll-like receptor 4 (TLR4) molecule. The TIR domain of TLR4 pdf format is tested against the isoquercetin molecule and analyzed using the docking software in a blinded fashion. The final image represents the drug (ball and stick structure, green) strongly bound to the protein having a Vina score of −7.2.