%0 Journal Article
%T Genetics of Cerebral Vasospasm
%A Travis R. Ladner
%A Scott L. Zuckerman
%A J Mocco
%J Neurology Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/291895
%X Cerebral vasospasm (CV) is a major source of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). It is thought that an inflammatory cascade initiated by extravasated blood products precipitates CV, disrupting vascular smooth muscle cell function of major cerebral arteries, leading to vasoconstriction. Mechanisms of CV and modes of therapy are an active area of research. Understanding the genetic basis of CV holds promise for the recognition and treatment for this devastating neurovascular event. In our review, we summarize the most recent research involving key areas within the genetics and vasospasm discussion: (1) Prognostic role of genetics¡ªrisk stratification based on gene sequencing, biomarkers, and polymorphisms; (2) Signaling pathways¡ªpinpointing key inflammatory molecules responsible for downstream cellular signaling and altering these mediators to provide therapeutic benefit; and (3) Gene therapy and gene delivery¡ªusing viral vectors or novel protein delivery methods to overexpress protective genes in the vasospasm cascade. 1. Introduction Cerebral vasospasm (CV) is the narrowing of the major cerebral arteries following aneurysmal subarachnoid hemorrhage (aSAH) and is a leading contributor to the morbidity and mortality associated with aSAH. The annual incidence of aSAH in the United States is between 21,000 and 33,000 people [1]. Of these, approximately 67% will develop vasospasm [2, 3]. In the setting of aSAH, CV has a biphasic course, with an acute and chronic phase. The acute phase typically begins 3 to 4 hours after hemorrhage, with rapid, spontaneous resolution. In contrast, the chronic phase begins 3 to 5 days later, with maximum narrowing between days 6 and 8, resolving after about 14 days [4]. CV can be diagnosed angiographically or clinically. Angiographic vasospasm refers to the observed narrowing of contrast medium in the major cerebral arteries. Radiologic modalities used to diagnose CV include computed tomography angiography (CTA), magnetic resonance angiography (MRA), and catheter angiography. Clinical vasospasm is the sequelae of neurocognitive deficits presumably as a result of a prolonged ischemic state. Both angiographic and clinical vasospasms can lead to cerebral infarction. Angiographic and clinical vasospasms appear to be distinct phenomena, with aSAH patients presenting with angiographic CV only (43% of patients), both angiographic and clinical CV (33% of patients), or none of them (24% of patients) [5]. Although there are many hypotheses on the pathogenesis of CV, it still remains a poorly understood
%U http://www.hindawi.com/journals/nri/2013/291895/