[Expression of p53 in neonatal mice following hypoxia-ischemia and effects of its inhibitor on neonatal brain injury].
OBJECTIVE
p53-induced apoptosis is crucial in the development of hypoxic-ischemia (HI) brain damage and neurodegenerative disorders. Some experimental research has shown that a synthetic inhibitor of p53 can protect neurons against apoptosis. This study aimed to explore the expression of p53 in neonatal mice following HI brain damage and the effect of p53 inhibitor (pifithrin-alpha, PFT-alpha) on brain damage.


METHODS
HI was induced in 9-day-old mice pups by ligation of left carotid artery and 10% oxygen exposure for 55 minutes. The pups were sacrificed and the brains were taken out at 3, 8, 24, and 72 hrs post-HI. The brains were sectioned and stained with antibody against p53 and microtubule-associated protein 2 (MAP-2). PFT-alpha was injected intraperitoneally: in experiment 1, immediately after HI with different dosages (1, 2 and 8 mg/kg); in experiment 2, 2 mg/kg at different HI times (1 hr before HI, and immediately and 1 hr after HI). Control animals without HI received injections of 0.5% dimethyl sulfoxide. Brain damage was evaluated by gross morphology scoring at 72 hrs after HI.


RESULTS
The number of p53 positive cells in the cortex, hippocampus and striatum of the ipsilateral hemisphere increased significantly and peaked at 3-8 hrs post-HI when compared with those of contralateral hemisphere as well as normal controls. The positive cells distributed mainly in the MAP-2 negative area. Both different dosages and different injection time PFT-alpha treatment did not reduce the extent of brain damage.


CONCLUSIONS
The immunoactivity of p53 increased significantly as early as 3 hrs post-HI. The distribution area of p53 expression was consistent with that of brain damage. The p53 inhibitor PFT-alpha has no protective effects against HI brain damage in neonatal mice.
Xu
Fa-Lin
FL
Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. xufalin72@126.com
Zhu
Chang-Lian
CL
Wang
Xiao-Yang
XY
Qiu
Lin
L
Ji
Ling
L
Cheng
Xiu-Yong
XY
Luan
Bin
B
D000818:Animals; D000831:Animals, Newborn; D052160:Benzothiazoles; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013844:Thiazoles / Q000494:pharmacology*; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000037:antagonists & inhibitors
D052160:Benzothiazoles; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin