Fumiaki Oka1,2, David Y Chung3,4, Michiyasu Suzuki5, Cenk Ayata3,4. 1. Neurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. oka6617@yamaguchi-u.ac.jp. 2. Department of Neurosurgery, Yamaguchi University School of Medicine, 1-1-1, Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. oka6617@yamaguchi-u.ac.jp. 3. Neurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. 4. Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. 5. Department of Neurosurgery, Yamaguchi University School of Medicine, 1-1-1, Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
Abstract
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.
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.
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