Cortical Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage: An Overview of Current Knowledge and Future Perspectives

Abstract

Despite significant advances in the management of aneurysmal subarachnoid hemorrhage (SAH), morbidity and mortality remain devastating particularly for high-grade SAH. Poor functional outcome usually results from delayed cerebral ischemia (DCI). The pathogenesis of DCI during aneurysmal SAH has historically been attributed to cerebral vasospasm, but spreading depolarizations (SDs) are now considered to play a central role in DCI. During SAH, SDs may produce an inverse hemodynamic response leading to spreading ischemia. Several animal models have contributed to a better understanding of the pathogenesis of SDs during aneurysmal SAH and provided new therapeutic approaches including N-methyl-D-aspartate receptor antagonists and phosphodiesterase inhibitors. Herein we review the current knowledge in the field of SDs' pathogenesis and we detail the key experimental and clinical studies that have opened interesting new therapeutic approaches to prevent DCI in aneurysmal SAH.

Keywords: Cerebral aneurysm; Delayed cerebral ischemia; Microcirculation; Spreading depolarization; Spreading ischemia; Subarachnoid hemorrhage.