%0 Journal Article
%T Matrix Metalloproteinases in Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage
%A Vivek Mehta
%A Jonathan Russin
%A Alexandra Spirtos
%A Shuhan He
%A Peter Adamczyk
%A Arun P. Amar
%A William J. Mack
%J Neurology Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/943761
%X Delayed cerebral vasospasm is a significant cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). While the cellular mechanisms underlying vasospasm remain unclear, it is believed that inflammation may play a critical role in vasospasm. Matrix metalloproteinasees (MMPs) are a family of extracellular and membrane-bound proteases capable of degrading the blood-rain barrier (BBB). As such, MMP upregulation following SAH may result in a proinflammatory extravascular environment capable of inciting delayed cerebral vasospasm. This paper presents an overview of MMPs and describes existing data pertinent to delayed cerebral vasospasm. 1. Background Delayed cerebral vasospasm is a devastating complication of subarachnoid hemorrhage (SAH). It typically occurs within fourteen days of aneurysmal rupture, and it is associated with significant morbidity and mortality [1, 2]. While pathophysiology remains incompletely understood, the interplay between inflammation and the innate immune response is strongly implicated. Following SAH, increased blood-brain barrier (BBB) permeability engenders a proinflammatory milieu in the cerebral cisterns and extravascular space. Subarachnoid blood initiates leukocyte transmigration via cellular margination, adhesion, rolling, and diapedesis [3]. The process necessitates violation of the tight junctions between endothelial cells of the BBB and typically occurs in response to stimulatory chemoattractants or chemokines. Coupled with concurrent physiologic derangements, these molecular alterations can incite delayed cerebral vasospasm. Regulation of the extracellular matrix and basal lamina by matrix metalloproteinase (MMP) enzymes may play a critical role in vasospasm. MMPs have been studied extensively in the pathogenesis of ischemic stroke and the development of aortic and cerebral aneurysms [4]. Recently, investigations have examined the role of MMPs in the setting of SAH. In this paper, we specifically review the function of MMPs in cerebral vasospasm. Understanding the complex interactions between inflammation and degradation of the extracellular matrix may ultimately allow for better development of diagnostic markers and targeted therapies relevant to the management of delayed cerebral vasospasm. 2. MMP Review MMPs are a family of extracellular and membrane-bound proteases capable of degrading or proteolytically modifying the extracellular matrix (ECM) through interactions with collagenases, laminins, and proteoglycans [5]. They utilize zinc-dependent endopeptidases to regulate physiologic
%U http://www.hindawi.com/journals/nri/2013/943761/