Evidence for the involvement of corticotrophin-releasing hormone in the pathogenesis of traumatic brain injury.
The aim of this study was to investigate the role of the neuropeptide corticotrophin-releasing hormone (CRH) in neurodegeneration induced by traumatic brain injury, using a well characterized model of lateral fluid percussion injury in male, Sprague-Dawley rats. In the first series of experiments, CRH gene expression was assessed by in situ hybridization after traumatic brain injury. A bilateral increase in CRH mRNA in the paraventricular nucleus was observed in rats subjected to traumatic brain injury compared with sham-operated controls. A maximal (40%) increase in hybridization signal was detected 2 h after trauma compared with control rat brains. In addition, marked induction of CRH transcripts was found in the ipsilateral amygdala after trauma, but no increase was detected in the ipsilateral cortex around the area of damage. In a separate experiment, the effects of the CRH antagonist, D-Phe CRH(12-41) (25 microg total dose), or appropriate vehicle injected intracerebroventricularly, was tested on infarct volume caused by brain injury. Repeated intracerebroventricular injection of D-Phe CRH(12-41) significantly reduced, by 45%, the volume of cortical damage in injured rats compared with vehicle-treated, trauma animals. The rapid upregulation of CRH gene expression in the paraventricular nucleus and amygdala following lateral fluid percussion injury and the marked neuroprotection achieved by inhibiting CRH action suggest that CRH is involved directly in the pathogenesis of traumatic brain injury. This observation may have important implications for the development of novel therapeutic strategies for treating the neurological consequences of brain trauma and related conditions.
Roe
S Y
SY
School of Biological Sciences, University of Manchester, UK.
McGowan
E M
EM
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001930:Brain Injuries / Q000473:pathology*; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006727:Hormone Antagonists; D010446:Peptide Fragments; C064461:corticotropin-releasing hormone (12-41), Phe(12)-Nle(21,38)-; D003346:Corticotropin-Releasing Hormone