Animal models of ischemic stroke and their impact on drug discovery

Area of Science:

• Neurology
• Pharmacology
• Translational Medicine

Background:

• Ischemic stroke is a primary cause of long-term disability, necessitating advancements in research and drug development.
• Current research focuses on identifying and validating reliable animal models for preclinical stroke studies.

Purpose of the Study:

• To review and summarize existing animal models of ischemic stroke suitable for drug discovery.
• To assess the utility of these models for evaluating acute and post-acute stroke treatments.
• To emphasize the importance of incorporating stroke-associated risk factors into preclinical models.

Main Methods:

• Review of existing literature on established animal models of permanent and transient focal cerebral ischemia in rodents.
• Analysis of occlusion methods, including mechanical devices, pharmacological agents, and clot delivery.
• Focus on models that incorporate age-related factors and vascular comorbidities relevant to human stroke.

Main Results:

• Reproducible models of focal cerebral ischemia exist in rats and mice, primarily involving middle cerebral artery occlusion.
• These models are valuable for assessing the efficacy of acute and post-acute stroke therapies.
• Models replicating stroke risk factors and spontaneous stroke offer greater clinical relevance.

Conclusions:

• Animal models must reliably mimic human stroke pathophysiology, risk factors, and drug treatment parameters for clinical relevance.
• Risk factor-inclusive models should be prioritized in early drug discovery and target identification phases.
• Improved animal models are crucial for advancing ischemic stroke drug development and patient outcomes.