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Increase in p53 protein expression following cortical infarction in the spontaneously hypertensive rat
1Department of Neurological Surgery, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, 791-0295 Ehime, Japan.
Abstract:
Using stroke-prone spontaneously hypertensive (SH-SP) rats with permanent occlusion of the middle cerebral artery (MCA), we investigated the expression of wild type p53 (wt-p53) protein and the occurrence of DNA fragmentation in cerebral neurons after ischemia. Three days following MCA occlusion, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL staining) revealed a distinct pattern of nuclear staining in many neurons around the ischemic core. On the lesioned side of the cerebral cortex one day after MCA occlusion, wt-p53 immunoreactivity was observed specifically in the cortical neurons, in the same regions as the TUNEL staining. Mutant type p53 (mt-p53) immunoreactivity was not observed at any time following MCA occlusion. These findings suggest that wt-p53 dependent cell death of cortical neurons occurred in the ischemic periphery following cerebral ischemia and that this pathway for the induction of cell death may play an important role in the exaggeration of cerebral ischemic injury.
Insights
Wild type p53 (wt-p53) protein expression and DNA fragmentation in brain neurons were studied after stroke in rats. Findings suggest wt-p53 dependent neuronal death contributes to stroke injury severity.
Area of Science:
- Neuroscience
- Pathology
Background:
- Cerebral ischemia, a leading cause of stroke, results in neuronal damage and death.
- The role of p53 protein in the neuronal cell death following ischemic stroke requires further elucidation.
Purpose of the Study:
- To investigate the expression of wild type p53 (wt-p53) and mutant type p53 (mt-p53) proteins.
- To examine the occurrence of DNA fragmentation in cerebral neurons after middle cerebral artery occlusion (MCAO).
Main Methods:
- Stroke-prone spontaneously hypertensive (SH-SP) rats underwent permanent middle cerebral artery occlusion (MCAO).
- Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL staining) was used to detect DNA fragmentation.
- Immunoreactivity for wt-p53 and mt-p53 proteins was assessed in cortical neurons.
Main Results:
- TUNEL staining revealed significant nuclear staining in neurons surrounding the ischemic core three days post-MCAO.
- Wt-p53 immunoreactivity was detected in cortical neurons on the lesioned side one day after MCAO, co-localizing with TUNEL staining.
- No mt-p53 immunoreactivity was observed at any time point after MCAO.
Conclusions:
- Wt-p53 dependent neuronal cell death occurs in the ischemic periphery following cerebral ischemia.
- The wt-p53 pathway may play a significant role in exacerbating cerebral ischemic injury.
- Targeting wt-p53 mediated cell death could be a potential therapeutic strategy for stroke.