Aggravation of ischemic brain injury by prion protein deficiency: Role of ERK-1/-2 and STAT-1

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• 作者：Annett Spudich ; Rico Frigg ; Ertugrul Kilic ; Ü ; lkan Kilic ; Bruno Oesch ; Alex Raeber ; Claudio L. Bassetti and Dirk M. Hermann
• 关键词：Middle cerebral artery occlusion ; Neuroprotection ; ERK-1/-2 ; STAT-1
• 刊名：Neurobiology of Disease
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：20
• 期：2
• 页码：442-449
• 全文大小：599 K

文摘

The cellular isoform of prion protein, PrP^c, may confer neuroprotection in the brain, according to recent studies. To elucidate the role of PrP^c in stroke pathology, we subjected PrP^c-knockout (Prnp^0/0), wild-type and PrP^c-transgenic (tga20) mice to 30 min of intraluminal middle cerebral artery occlusion, followed by 3, 24 or 72 h reperfusion, and examined how PrP^c levels influence brain injury and cell signaling. In immunohistochemical experiments and Western blots, we show that PrP^c expression is absent in the brains of Prnp^0/0 mice, detectable in wild-type controls and 4.0-fold elevated in tga20 mice. We provide evidence that PrP^c deficiency increases infarct size by 200 % , while transgenic PrP^c restores tissue viability, albeit not above levels in wild-type animals. To elucidate the mechanisms underlying Prnp^0/0-induced injury, we performed Western blots, which revealed increased activities of ERK-1/-2, STAT-1 and caspase-3 in ischemic brains of Prnp^0/0 mice. Our data suggest a role of cytosolic signaling pathways in Prnp^0/0-induced cell death.