TITLE:
Neuroprotection in Acute Ischemic Stroke: Pathological Mechanisms and Reflections on Translation from Bench to Bedside
AUTHORS:
Renhui Yan, Junfeng Su
KEYWORDS:
Acute Ischemic Stroke, Neuroprotection, Programmed Cell Death, Excitotoxicity, Neuroinflammation, Oxidative Stress, Ischemia-Reperfusion Injury
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.10,
October
27,
2026
ABSTRACT: Acute ischemic stroke is a leading cause of death and disability worldwide. Interruption of cerebral perfusion caused by arterial occlusion triggers a cascade of ischemic brain injury, imposing a substantial burden on public health systems. Intravenous thrombolysis and mechanical thrombectomy are currently the evidence-based reperfusion therapies; however, owing to constraints such as a narrow therapeutic time window, hemorrhagic transformation, and ischemia-reperfusion injury, many patients still suffer severe neurological deficits. Post-ischemic excitotoxicity, neuroinflammation, and oxidative stress are intertwined and collectively drive multiple forms of programmed cell death—including apoptosis, necroptosis, pyroptosis, and ferroptosis—thereby mediating progressive neuronal loss in the ischemic penumbra. Deciphering this pathological network is a core prerequisite for developing neuroprotective strategies. Although numerous preclinical studies have demonstrated that drugs, nanodelivery systems, stem cells/exosomes, and physical interventions targeting these pathways can exert neuroprotective effects, the vast majority of these strategies have not yet achieved clear, independent benefit in human clinical trials. With the widespread adoption of endovascular reperfusion therapy, neuroprotection is regarded as an important breakthrough in the management of acute ischemic stroke. This review systematically summarizes the key pathophysiological processes and various programmed cell death mechanisms after acute ischemic stroke, outlines the current status of interventions targeting different targets, and analyzes the practical obstacles to bench-to-bedside translation, aiming to provide a reference for the development of novel neuroprotective strategies.