The tumor-suppressor gene, p53, is induced in injured brain regions following experimental traumatic brain injury.
A growing body of evidence suggests that neurons undergo apoptotic cell death following traumatic brain injury (TBI). Since the expression of several tumor suppressor and cell cycle genes have been implicated in neuronal apoptosis, the present study used in situ hybridization (ISH) histochemistry to evaluate the regional and temporal patterns of expression of the mRNAs for the tumor suppressor gene, p53, and the cell cycle gene, cyclin D1, following lateral fluid-percussion (FP) brain injury in the rat. Anesthetized adult male Sprague-Dawley rats (n=16) were subjected to lateral FP brain injury of moderate severity (2.4-2.7 atm), while sham controls (n=6) were surgically prepared but did not receive brain injury. Animals were killed by decapitation at 6 h (n=6 injured and 2 sham), 24 h (n=6 injured and 2 sham), or 3 days (n=4 injured and 2 sham), and their brains processed for ISH. Little to no expression of p53 mRNA was observed in sham brains. At 6 h post-injury, p53 mRNA was induced predominantly in cells that are vulnerable to TBI, such as those in the contused cortex, lateral and medial geniculate nuclei of the thalamus, and the CA(3) and hilar neurons of the hippocampus. Increased p53 mRNA was also detected in hippocampal CA(1) neurons, cells that are relatively resistant to FP brain injury. Levels of p53 mRNA returned to sham levels in all regions of the injured brain by 24 h. In contrast to p53, cyclin D1 mRNA was detectable in the brains of uninjured animals and was not altered by brain injury. These results suggest that the tumor suppressor gene p53, but not cyclin D1, is upregulated and may participate in molecular response to TBI.
Department of Neurosurgery, University of Pennsylvania School of Medicine, 105B Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104, USA.
J A
JA
Napieralski
R
R
Raghupathi
T K
TK
McIntosh
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D007839:Functional Laterality; D005786:Gene Expression Regulation; D016158:Genes, p53; D005829:Geniculate Bodies / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013788:Thalamus / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53