Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Experimental-Clinical Disconnect and the Unmet Need

Area of Science:

• Neuroscience
• Translational Medicine
• Critical Care

Background:

• Delayed cerebral ischemia (DCI) is a major complication of aneurysmal subarachnoid hemorrhage (SAH), leading to significant morbidity and mortality.
• Classical theories implicating large artery vasospasm in DCI are increasingly challenged by clinical trial failures.
• Emerging research focuses on microvascular dysfunction and spreading depolarizations as alternative DCI mechanisms.

Purpose of the Study:

• To systematically review existing animal models of SAH.
• To evaluate their capacity to reproduce delayed cerebral ischemia (DCI) and associated neurological deficits.
• To identify the translational relevance of these models for understanding SAH pathophysiology.

Main Methods:

• Systematic literature review of animal models of subarachnoid hemorrhage (SAH).
• Focus on studies reporting delayed cerebral ischemia (DCI) and neurological deficits.
• Analysis of model efficacy, reliability, and translational utility.

Main Results:

• Non-primate models (dog, rabbit, rodent) often fail to consistently induce DCI, though some vascular dysfunction is observed.
• Primate models effectively replicate DCI, neurological deficits, and ischemic brain injury.
• Ethical concerns and high costs limit the clinical applicability of primate models.

Conclusions:

• Existing animal models for SAH exhibit limitations in reliably recapitulating DCI.
• Primate models show higher translational relevance but face practical constraints.
• Development of clinically applicable animal models is essential for advancing DCI research and treatment.