Apoptosis and the Expression of p53, Bcl-2 in Very Delayed Focal Cerebral Infarction and Penumbra

Chung, Chan; Park, Seung Won; Kim, Young Baeg; Hwang, Sung Nam; Kim, Mi Kyung; Kwon, Jeong Taik; Min, Byung Kook; Suk, Jong Sik; Choi, Duck Young

Abstract

Apoptosis is a physiological or programmed cell death process controlled by genes, which is thought to be one of the main mechanisms of cell death in cerebral infarction. The apoptosis is controlled by several protooncogenes including p53 and Bcl-2 genes. The purpose of this study is to evaluate how the apoptotic genes express in the focal cerebral infarction and penumbra at very delayed focal cerebral infarction in adult rats. In twelve adult Sprague-Dawley rats of both sex, the right middle cerebral artery(MCA) and both common carotid arteries were ligated for thirty minutes and the rats were killed after seventy-two hours to obtain a focal cerebral infarction. Immunohistochemical stains for the apoptosis, p53, and Bcl-2 proteins were performed. The thickness (micrometer) and the area(mm2) of the infarction core and periinfarct areas containing apoptotic cells, p53, or Bcl-2 protein were measured. The apoptosis, p53, and Bcl-2 positive cells were counted, and the p53: Bcl-2 ratio was calculated at each sector. The p53 area was the widest(6.8+/-2.4mm2) and the apoptosis area was the narrowest(3.1+/-2.1mm2). The apoptotic cells were mostly concentrated in the peripheral portion of the infarction core(6.1+/-3.7/HPF). The p53 positive cells were mostly concentrated(26.6+/-8.0/HPF) in the adjacent periinfarct area with a gradual decrease peripherally, and it seemed that p53 expression was reversely proportional to the regional cerebral blood flow(rCBF). The p53: Bcl-2 ratio was significantly higher at the apoptosis-positive zone(3.3+/-2.7) compared with the apoptosis-negative zone(2.2+/-1.8)(p<0.05). From these results, it could be postulated that the proapoptotic action of the p53 protein and the antiapoptotic action of Bcl-2 protein were closely interactive in the periinfarct area. These data indicate that the p53 protein positive area might be compatible with the penumbric area of cerebral infatction.