Purpose
The physiological role of the cellular isoform of prion protein, PrPc, is largely unknown. It has recently been suggested that PrPc may confer neuroprotection in the brain, possibly via anti-oxidative actions. The aim of this study was to define the role of PrPc in the pathophysiology of ischemic stroke.
Methods
PrPc knockout (Prnp0/0), wild-type and PrPc-transgenic (tga20) mice were subjected to 30 minutes of intraluminal middle cerebral artery (MCA) occlusion. Brain injury and cell signalling were assessed at 24 and 72 hours of reperfusion.
Results
In immunohistochemical experiments we show that PrPc expression is absent in the brains of Prnp0/0 mice, detectable in wild-type controls and elevated in tga20 mice. We provide evidence that PrPc deficiency increases infarct size by ∼200%, while transgenic PrPc restores tissue viability, albeit not above levels in wild-type animals. To elucidate the mechanisms underlying Prnp0/0-induced injury, we performed Western blots, which revealed increased activities of STAT-1, ERK-1/-2, JNK-1/-2 and caspase-3 in ischemic brains of Prnp0/0 mice, but no differences between wild-type and tga20 animals.
Conclusions
Whereas Prnp0/0 massively increases ischemic brain injury, the elevated PrPc expression in transgenic tga20 mice does not confer additional neuroprotection, when compared with wild-type animals. Elevated levels of STAT-1, ERK-1/-2, JNK-1/-2 and caspase-3 activities in PrPc deficient mice suggest a role of tyrosine kinases in Prnp0/0-induced cell death.