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

Background Delayed cerebral ischemia (DCI) is among the most dreaded complications following aneurysmal subarachnoid hemorrhage (SAH). Despite advances in neurocritical care, DCI remains a significant cause of morbidity and mortality, prolonged intensive care unit and hospital stay, and high healthc...

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Bibliographic Details
Published in:Neurocritical care 2020-02, Vol.32 (1), p.238-251
Main Authors: Oka, Fumiaki, Chung, David Y., Suzuki, Michiyasu, Ayata, Cenk
Format: Article
Language:English
Subjects:
Animals
Brain Ischemia - etiology
Brain Ischemia - physiopathology
Cell death
Critical Care Medicine
Disease Models, Animal
Dogs
Hemorrhage
Injections
Intensive
Internal Medicine
Ischemia
Kinases
Medicine
Medicine & Public Health
Mice
Neurology
Primates
Rabbits
Rats
Review Article
Subarachnoid Hemorrhage - complications
Subarachnoid Hemorrhage - physiopathology
Vasospasm, Intracranial - etiology
Vasospasm, Intracranial - physiopathology
Veins & arteries
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Summary:Background Delayed cerebral ischemia (DCI) is among the most dreaded complications following aneurysmal subarachnoid hemorrhage (SAH). Despite advances in neurocritical care, DCI remains a significant cause of morbidity and mortality, prolonged intensive care unit and hospital stay, and high healthcare costs. Large artery vasospasm has classically been thought to lead to DCI. However, recent failure of clinical trials targeting vasospasm to improve outcomes has underscored the disconnect between large artery vasospasm and DCI. Therefore, interest has shifted onto other potential mechanisms such as microvascular dysfunction and spreading depolarizations. Animal models can be instrumental in dissecting pathophysiology, but clinical relevance can be difficult to establish. Methods Here, we performed a systematic review of the literature on animal models of SAH, focusing specifically on DCI and neurological deficits. Results We find that dog, rabbit and rodent models do not consistently lead to DCI, although some degree of delayed vascular dysfunction is common. Primate models reliably recapitulate delayed neurological deficits and ischemic brain injury; however, ethical issues and cost limit their translational utility. Conclusions To facilitate translation, clinically relevant animal models that reproduce the pathophysiology and cardinal features of DCI after SAH are urgently needed.
ISSN:1541-6933
1556-0961
DOI:10.1007/s12028-018-0650-5