title: Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage.
abstract: A growing body of clinical literature emphasizes the impact of cerebral edema in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Aneurysm rupture itself initiates global cerebral edema in up to two thirds of cases. Although cerebral edema is not a universal feature of aSAH, it portends a poor clinical course, with quantitative analysis revealing a direct correlation between cerebral edema and poor outcome, including mortality and cognitive deficits. Mechanistically, global cerebral edema has been linked to global ischemia at the time of aneurysm rupture, dysfunction of autoregulation, blood breakdown products, neuroinflammation, and hyponatremia/endocrine abnormalities. At a molecular level, several culprits have been identified, including aquaporin-4, matrix metalloproteinase-9, SUR1-TRPM4 cation channels, vascular endothelial growth factor, bradykinin, and others. Here, we review these cellular and molecular mechanisms of global cerebral edema formation in aSAH. Given the importance of edema to the outcome of patients with aSAH and its status as a highly modifiable pathological process, a better understanding of cerebral edema in aSAH promises to hasten the development of medical therapies to improve outcomes in this frequently devastating disease.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Hayman
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Wessell
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
authors.affiliation: Department of Neurology, Yale New Haven Hospital, New Haven, CT, USA.|Department of Neurosurgery, Yale New Haven Hospital, New Haven, CT, USA.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sheth
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA. msimard@som.umaryland.edu.|Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA. msimard@som.umaryland.edu.|Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA. msimard@som.umaryland.edu.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology*; D006801:Humans; D013345:Subarachnoid Hemorrhage / Q000150:complications*
keywords: Edema; Keywords; Subarachnoid hemorrhage