title: An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage.
abstract: Cerebral vasospasm and the resulting cerebral ischemia occurring after subarachnoid hemorrhage (SAH) are still responsible for the considerable morbidity and mortality in patients affected by cerebral aneurysms. Mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia after SAH have been intensively investigated in recent years. It has been suggested that the pathogenesis of vasospasm is related to a number of pathological processes, including endothelial damage, smooth muscle cell contraction resulting from spasmogenic substances generated during lyses of subarachnoid blood clots, changes in vascular responsiveness and inflammatory or immunological reactions of the vascular wall. A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent these complications. However, to date, the main therapeutic interventions remain elusive and are limited to the manipulation of systemic blood pressure, alteration of blood volume or viscosity, and control of arterial dioxide tension. Even though no single pharmacological agent or treatment protocol has been identified which could prevent or reverse these deadly complications, a number of promising drugs have been investigated. Among these is the hormone erythropoietin (EPO), the main regulator of erythropoiesis. It has recently been found that EPO produces a neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systemically administered. This topic review collects the relevant literature on the main investigative therapies for cerebrovascular dysfunction after aneurysmal SAH. In addition, it points out rHuEPO, which may hold promise in future clinical trials to prevent the occurrence of vasospasm and cerebral ischemia after SAH.
authors.affiliation: Department of Neurosurgery, University of Messina, Via C. Valeria 1, 98122, Messina, Italy. Giovanni.Grasso@unime.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grasso
mesh_terms: D000818:Animals; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D011994:Recombinant Proteins; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D016232:Endothelins; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D011994:Recombinant Proteins; D004921:Erythropoietin