title: Effect of secondary insults upon aquaporin-4 water channels following experimental cortical contusion in rats.
abstract: Although secondary insults of hypoxia and hypotension (HH) are generally considered to cause fulminant brain edema in traumatic brain injury (TBI), the combined effect of TBI with HH on brain edema and specifically the expression of aquaporin-4 (AQP4) have not been fully elucidated. The goal of this study was to document the effect of secondary insults on brain water, AQP4 expression, electrolytes, and blood-brain barrier (BBB) permeability during the acute stage of edema development. We measured brain water content and electrolytes (series 1); BBB permeability based on Evans blue (EB) dye extravasation (series 2); and AQP4 expression using immunoblotting (series 3) at 1 h and 5 h following cortical contusion injury (CCI). Secondary insults significantly worsened BBB function at 5 h post injury. Moreover, a significant reduction of upregulation on AQP4 expression was observed in trauma, coupled with a mild secondary insult of hypoxia hypotension. These findings indicate that a secondary insult following CCI at 5 h post injury worsens brain edema, disrupts ionic homeostasis, and blunts the normal upregulation of AQP4 that occurs after trauma, suggesting that the blunting of AQP4 may contribute to the detrimental effects of secondary insults.
authors.affiliation: Department of Neurosurgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia 23298-0508, USA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taya
authors.forename: Christina R
authors.initials: CR
authors.lastname: Marmarou
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuno
authors.forename: Ruth
authors.initials: R
authors.lastname: Prieto
authors.forename: Anthony
authors.initials: A
authors.lastname: Marmarou
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004573:Electrolytes / Q000378:metabolism; D005070:Evans Blue / Q000493:pharmacokinetics; D007022:Hypotension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D004573:Electrolytes; D007202:Indicators and Reagents; D005070:Evans Blue
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