Prion protein accumulation and neuroprotection in hypoxic brain damage

The function of the normal conformational isoform of prion protein, PrPC, remains unclear although lines of research have suggested a role in the cellular response to oxidative stress. Here we investigate the expression of PrPC in hypoxic brain tissues to examine whether PrPC is in part regulated by neuronal stress. Cases of adult cerebral ischemia and perinatal hypoxic-ischemic injury in humans were compared with control tissues. PrPC immunoreactivity accumulates within neuronal processes in the penumbra of hypoxic damage in adult brain, and within neuronal soma in cases of perinatal hypoxic-ischemic injury, and in situ hybridization analysis suggests an up-regulation of PrP mRNA during hypoxia. Rodents also showed an accumulation of PrPC in neuronal soma within the penumbra of ischemic lesions. Furthermore, the infarct size in PrP-null mice was significantly greater than in the wild type, supporting the proposed role for PrPC in the neuroprotective adaptive cellular response to hypoxic injury.