Prokineticins are neuroprotective in models of cerebral ischemia and ischemic tolerance in vitro

摘要: Abstract Bv8/prokineticin 2 (PK2) is a member of bioactive family peptides that regulate multiple functions in the CNS including hyperalgesia, neurogenesis, neuronal survival and inflammation. Recent studies have associated PK2 prokineticin receptors (PKR) with human diseases, but because their role neuropathology still debated we examined whether prokineticins exert protective or deleterious models cerebral ischemia ischemic tolerance in vitro. In order to mimic ischemia, exposed primary murine cortical cell cultures rat organotypic hippocampal slices appropriate periods oxygen-glucose deprivation (OGD), which leads damage 24 h later. Ischemic was induced by exposing preconditioning subtoxic pharmacological stimulus (3 μM NMDA for 1 h) before exposure OGD. Bv8 (10–100 nM) attenuated OGD injury slices, effect prevented PKR antagonist PC7. The development an increase expression PK2, PKR1 PKR2 mRNA proteins addition PC7 into medium during preconditioning. Both at concentrations promoted phosphorylation ERK1/2 Akt. These findings indicate system can be up-regulated defensive may act as endogenous neuroprotective factor through activation Akt transduction pathways.