Postinjury magnesium treatment attenuates traumatic brain injury-induced cortical induction of p53 mRNA in rats.
Administration of magnesium has been shown to be neuroprotective in experimental models of traumatic brain injury (TBI). The present study examined the effect of magnesium on posttraumatic regional induction of p53, a gene associated with induction of cell death. Male Sprague-Dawley rats (350-400 g, n = 26) were anesthetized with sodium pentobarbital and subjected to either lateral fluid percussion brain injury of moderate severity (2.4-2.6 atm; n = 22) or sham surgery (n = 4). At 15 min postinjury, animals randomly received an intravenous bolus of either 125 micromol magnesium chloride (n = 12) or saline vehicle (n = 10). Expression of p53 mRNA was not observed in any uninjured animal. By 6 h postinjury in vehicle-treated, brain-injured animals, p53 mRNA was induced in the cortex, dentate hilus, and CA3 regions of the hippocampus and geniculate nuclei of the thalamus, ipsilateral to the impact site. Posttraumatic magnesium treatment significantly reduced the number of labeled cells in the injured cortex (P < 0.05), but not in the hippocampus or thalamus. p53 mRNA expression returned to near baseline in all animals by 24 h postinjury. These data suggest that the neuroprotective effects of magnesium treatment may be related, in part, to a downregulation in expression of a gene associated with induction of cell death and further support the utility of magnesium as a pharmacotherapy for TBI.
Muir
J K
JK
School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Raghupathi
R
R
Emery
D L
DL
Bareyre
F M
FM
McIntosh
T K
TK
D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D016158:Genes, p53; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D015636:Magnesium Chloride