Exploration of non-clinical pharmacodynamics evaluation system of ischemic stroke

Ischemic stroke (IS) remains a leading cause of mortality and disability among adults worldwide, with its core pathological mechanism rooted in ischemic-hypoxic neuronal injury triggered by cerebral blood flow interruption. Current clinical treatments primarily rely on intravenous thrombolysis and endovascular thrombectomy. However, these approaches are constrained by strict therapeutic time windows (typically ≤ 4.5 h), bleeding risks in certain patients, and limited neurorestorative effects following reperfusion. Despite active development of neuroprotective agents and anti-inflammatory drugs in recent years, most have failed in clinical translation due to insufficient efficacy or safety concerns, highlighting the complexity of disease mechanisms and limitations of preclinical evaluation systems. Consequently, developing therapeutics that simultaneously address reperfusion protection and neural repair by targeting the pathological cascade of IS has emerged as a critical direction to overcome current therapeutic bottlenecks. This review synthesizes recent advances in domestic and international IS drug development in recent years, focusing on model establishment, efficacy evaluation metrics, and relevant molecular mechanisms to systematically summarize the preclinical pharmacodynamic evaluation framework for IS therapeutics. The findings provide valuable insights for optimizing preclinical evaluation systems, accelerating drug development, and expanding effective clinical treatment strategies for IS.