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: Changping Yao, Guo Wei, X-C May Lu, Weihong Yang, Frank C Tortella, Jitendra R Dave
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 28 Issue 7 Pg. 1237-45 (Jul 2011) ISSN: 1557-9042 [Electronic] United States
• PMID: 21463155 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Heme
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Animals
• Body Water (metabolism)
• Brain Edema (enzymology, physiopathology, therapy)
• Cerebral Hemorrhage (enzymology, physiopathology, therapy)
• Disease Models, Animal
• Down-Regulation (physiology)
• Head Injuries, Penetrating (complications, enzymology, therapy)
• Heme (antagonists & inhibitors, metabolism)
• Heme Oxygenase (Decyclizing) (biosynthesis, genetics, physiology)
• Hypothermia, Induced (methods)
• Male
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (physiology)