The Role of Cortical Spreading Depolarizations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Abstract

Delayed cerebral ischemia (DCI) is the leading potentiallytreatable cause of mortality and disability in patients with aneurysmal subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on DCI that follows SAH. DCI was long believed the consequence of the angiographically visible arterial spasm observed in patients with SAH. Since the measurement of cortical spreading depolarizations (CSD) in patients with SAH, increasing evidence has suggested a role for these phenomena in the pathophysiology of DCI. When inducedin a healthy brain, CSDs are associated with an increasein regional cerebral blood flow that facilitates the delivery ofthe necessary energy substrates for cellular repolarization. In a brain that has been injured, however, CSDs can induce microvascular constriction, or cortical spreading ischemia. This inverse hemodynamic response to CSD was first discovered in an animal model replicating the conditions following SAH, and later demonstrated in patients with SAH. The spreading ischemia leads to energy substrates shortage and hypoxia, resulting in cortical lesions, and may explain similar lesion patterns which occur in SAH patients. This review describes the salient characteristics of CSD and its potential relevance in the pathophysiology, monitoring, and treatment of ischemic complications following SAH.