医学
恶化
缺血性损伤
蛋白激酶B
细胞凋亡
创伤性脑损伤
小胶质细胞
半胱氨酸蛋白酶
朊蛋白
神经炎症
半胱氨酸蛋白酶3
缺血
神经科学
免疫学
病理
程序性细胞死亡
炎症
内科学
疾病
生物化学
精神科
化学
生物
作者
Jens Weise,Raoul Sandau,Sönke Schwarting,Olaf Crome,Arne Wrede,Walter Schulz‐Schaeffer,Inga Zerr,Mathias Bähr
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2006-05-01
卷期号:37 (5): 1296-1300
被引量:172
标识
DOI:10.1161/01.str.0000217262.03192.d4
摘要
The physiological function of cellular prion protein (PrPc) is not yet understood. Recent findings suggest that PrPc may have neuroprotective properties, and its absence increases susceptibility to neuronal injury. The purpose of this study was to elucidate the role of PrPc in ischemic brain injury in vivo.PrP knockout (Prnp(0/0)) and Prnp(+/+) wild-type (WT) mice were subjected to 60-minute transient or permanent focal cerebral ischemia followed by infarct volume analysis 24 hours after lesion. To identify effects of PrPc deletion on mechanisms regulating ischemic cell death, expression analysis of several proapoptotic and antiapoptotic proteins was performed at 6 and 24 hours after transient ischemia and in nonischemic controls using Western blot or immunohistochemistry.Prnp(0/0) mice displayed significantly increased infarct volumes after both transient or permanent ischemia when compared with WT animals (70.2+/-23 versus 13.3+/-4 mm3; 119.8+/-24 versus 86.4+/-25 mm3). Expression of phospho-Akt (Ser473) was significantly reduced in Prnp(0/0) compared with WT animals both early after ischemia and in sham controls. Furthermore, postischemic caspase-3 activation was significantly enhanced in the basal ganglia and the parietal cortex of Prnp(0/0) mice. In contrast, expression of total Akt, Bax, and Bcl-2 did not differ between both groups.These results demonstrate that PrPc deletion impairs the antiapoptotic phosphatidylinositol 3-kinase/Akt pathway by resulting in reduced postischemic phospho-Akt expression, followed by enhanced postischemic caspase-3 activation, and aggravated neuronal injury after transient and permanent cerebral ischemia.
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