title: Hypothetical roles of angiogenesis, osmotic swelling, and ischemia in high-altitude cerebral edema.
abstract: High-altitude cerebral edema (HACE) has been tentatively attributed to either cellular ion pump failure from ATP depletion or high cerebral blood flow inducing high capillary pressure. These hypotheses are inadequate because 1) ATP decrease occurs only after anoxia has silenced neuronal activity and 2) prolonged hypercapnic hyperemia generates only minor transcapillary protein leakage localized to the less hyperemic brain regions. In connection with this review of HACE and its causes, three other hypothetical mechanisms that might contribute are presented. 1) Osmotic cell swelling: cellular and mitochondrial osmotic pressure may rise 30 mosmol in ischemia or anoxia (potentially a 7-10% expansion). Smaller rises caused by hypoxia may be significant in the closed calvarium. 2) Focal ischemia: this may result from intracranial hypertension from hyperemia and osmotic swelling. 3) Angiogenesis: cellular hypoxia initially attracts and activates macrophages that express vascular endothelial growth factor and other cytokines, dissolving capillary basement membranes and degrading extracellular matrix, resulting in capillary leakage. In HACE, petechial hemorrhages are seen in the nerve cell layers of the retina, and similar changes have been described throughout the brain. Evidence linking HACE to angiogenesis is that dexamethasone, an effective inhibitor of angiogenesis, has demonstrated unique success in preventing and treating HACE.
authors.affiliation: Department of Anesthesia, University of California Medical School, San Francisco 94143-0542, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Severinghaus
mesh_terms: D000532:Altitude Sickness / Q000503:physiopathology*; D000818:Animals; D001929:Brain Edema / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009994:Osmolar Concentration