title: Selective brain cooling in rats ameliorates intracerebral hemorrhage and edema caused by penetrating brain injury: possible involvement of heme oxygenase-1 expression.
abstract: Brain edema formation associated with trauma-induced intracerebral hemorrhage (ICH) is a clinical complication with high mortality. Studies have shown that heme oxygenase-1 (HO-1) plays an important role in ICH-induced brain edema. In order to understand the role of HO-1 in the protective effect of selective brain cooling (SBC), we investigated the time course of HO-1 changes following penetrating ballistic-like brain injury (PBBI) in rats. Samples were collected from injured and control animals at 6, 24, 48, and 72 h, and 7 days post-injury to evaluate HO-1 expression, heme concentration, brain water content, and immunohistochemistry (IHC). Following a 10% frontal PBBI, HO-1 mRNA and protein was increased at all time points studied, reaching maximum expression levels at 24-48 h post-injury. An increase in the heme concentration and the development of brain edema coincided with the upregulation of HO-1 mRNA and protein during the 7-day post-injury period. SBC significantly decreased PBBI-induced heme concentration, attenuated HO-1 upregulation, and concomitantly reduced brain water content. These results suggest that the neuroprotective effects of SBC may be partially mediated by reducing the heme accumulation, which reduced injury-mediated upregulation of HO-1, and in turn ameliorated edema formation. Collectively, these results suggest a potential value of HO-1 as a diagnostic and/or therapeutic biomarker in hemorrhagic brain injury.
authors.affiliation: Department of Applied Neurobiology, Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant AvenueSilver Spring, MD 20910, USA.
authors.forename: Changping
authors.initials: C
authors.lastname: Yao
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.forename: X-C May
authors.initials: XC
authors.lastname: Lu
authors.forename: Weihong
authors.initials: W
authors.lastname: Yang
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Jitendra R
authors.initials: JR
authors.lastname: Dave
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D001929:Brain Edema / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy*; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D020197:Head Injuries, Penetrating / Q000150:complications / Q000201:enzymology* / Q000628:therapy*; D006418:Heme / Q000037:antagonists & inhibitors / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat