Molecular Keys to the Problems of Cerebral Vasospasm

Abstract

The mechanisms responsible for subarachnoid hemorrhage (SAH)-induced vasospasm are under intense investigation but remain incompletely understood. A consequence of SAH-induced vasospasm, cerebral infarction, produces a nonrecoverable ischemic tissue core surrounded by a potentially amenable penumbra. However, successful treatment has been inconsistent. In this review, we summarize the basic molecular biology of cerebrovascular regulation, describe recent developments in molecular biology to elucidate the mechanisms of SAH-induced vasospasm, and discuss the potential contribution of cerebral microcirculation regulation to the control of ischemia. Our understanding of the pathogenesis of SAH-induced vasospasm remains a major scientific challenge; however, molecular biological techniques are beginning to uncover the intracellular mechanisms involved in vascular regulation and its failure. Recent findings of microvascular regulatory mechanisms and their failure after SAH suggest a role in the development and size of the ischemia. Progress is being made in identifying the various components in the blood that cause SAH-induced vasospasm. Thus, our evolving understanding of the underlying molecular mechanism may provide the basis for improved treatment after SAH-induced vasospasm, especially at the level of the microcirculation.

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

“…Thus, it appears that a combination of oxidative stress and high bilirubin are required to produce BOXes, which in turn produce SAH-induced vasospasm. This multifactorial requirement (for increased oxidative stress and increased bilirubin) being necessary for BOXes production and the induction of vasospasm is consistent with the published data, suggesting that multiple factors may contribute to SAH-induced cerebral vasospasm (Dietrich and Dacey, 2000;Janjua and Mayer, 2003;Kaye et al, 1984;Lanterna et al, 2005;Macdonald et al, , 2004Weir, 1991, 1994;Pluta, 2005;Sobey and Faraci, 1998;Zimmermann and Seifert, 1998).…”

“…The delayed vasospasm that occurs after subarachnoid hemorrhage (SAH) has been the subject of multiple studies, continuing controversies, and a continuing search for the substance or substances that cause this clinically frustrating disease (Dietrich and Dacey, 2000;Janjua and Mayer, 2003;Weir, 1991, 1994;Megyesi et al, 2000;Pluta, 2005;Roux et al, 1999). Once patients survive the initial SAH, and often have had the aneurysm adequately addressed by surgical and/or radiologi means, some patients develop vasospasm and have a stroke (sometimes referred to as a delayed neurologic ischemic deficit-DIND), by still unknown mechanisms (Dietrich and Dacey, 2000;Janjua and Mayer, 2003;Weir, 1991, 1994;Megyesi et al, 2000;Pluta, 2005;Roux et al, 1999).…”

“…Once patients survive the initial SAH, and often have had the aneurysm adequately addressed by surgical and/or radiologi means, some patients develop vasospasm and have a stroke (sometimes referred to as a delayed neurologic ischemic deficit-DIND), by still unknown mechanisms (Dietrich and Dacey, 2000;Janjua and Mayer, 2003;Weir, 1991, 1994;Megyesi et al, 2000;Pluta, 2005;Roux et al, 1999). This review summarizes the evidence that oxidized forms of bilirubin cause or contribute to vasospasm associated with SAH.…”

Management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

“…2,15 These trapped cells undergo degranulation and release of inflammatory factors, like endothelin and free radicals; this inflammatory process induces arterial vasoconstriction. 2,15 There are two phases of this inflammatory process, an initial or acute phase occurs 1-3 days after the primary injury, 16 mediated by macrophages and neutrophils, and a delayed phase, mediated by inflammatory products from degranulation of the acute phase cells, occurs in days to weeks. 2 Cortical spreading depression (CSD) or cortical depolarization is a phenomenon described in several neurological injuries.…”

Reversible cerebral vasoconstriction syndrome: current and future perspectives

“…Blood pressure surge [12,15], triggers with elevated sympathetic tone [12,15], ingestion of sympathomimetic vasoactive substances [10,14,15,17], pheochromocytoma [40][41][42] and acute hypertensive crises [43] all support the role of sympathetic overactivity. In addition, it is hypothesized that some of the immunologic and biochemical factors known to regulate vascular tone in the delayed vasospasm in SAH might also be important in the pathophysio logy of vasoconstriction in RCVS [44][45][46], although direct evidences are lacking. Recently, the BDNF Val66Met polymorphism has been linked to vaso constriction in patients with RCVS [18].…”