Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity

The pathological isoform of the prion protein (PrPSc) has been identified to mediate transmissible spongiform encephalopathies like Creutzfeldt-Jakob disease (CJD). In contrast, the physiological function of the normal cellular prion protein (PrPc) is not yet understood. Recent findings suggest that PrPc may have neuroprotective properties and that its absence increases susceptibility to oxidative stress and neuronal injury. To determine whether PrPc is part of the cellular response to neuronal injury in vivo, we investigated PrPc regulation after severe and mild focal ischemic brain injury in mice using the thread occlusion stroke model. Western Blot and ELISA analysis showed a significant upregulation of PrPc in the ischemic hemisphere at 4 and 8 h after onset of permanent focal ischemia, which was no longer detectable at 24 h after lesion induction when compared to control animals. In contrast, transient focal ischemia (60 min) did only lead to slightly but not significantly elevated PrPc levels in the ischemic hemisphere when compared to controls. These results demonstrate that cerebral PrPc is upregulated early in response to focal cerebral ischemia. The extent of upregulation, however, seems to depend on the severity of ischemia and may therefore reflect the extent of ischemia induced neuronal damage. Given the known neuroprotective effects of PrPc in vitro, ischemia-induced upregulation of cerebral PrPc supports the hypothesis that, as part of an early adaptive cellular response to ischemic brain injury, PrPc may be involved in the regulation of ischemia-induced neuronal cell death in vivo. (C) 2004 Elsevier Ireland Ltd. All rights reserved.