Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals.

ABSTRACT

Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective effects in various in vitro and in vivo models of cerebral pathologies. It has been shown that PACAP protects neurons in rat models of both global and focal ischemia. In the present study, we investigated factors that may play a role in the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin-induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell line (A126). This effect was also observed in vivo, in permanent occlusion of the middle cerebral artery, where the number of TUNEL-positive neurons was significantly reduced in the ischemic core of PACAP-treated animals. Our results show that PACAP has a minor antioxidant effect in a non-cellular in vitro system, and has considerable antioxidant effects in an in vitro red blood cell filtration model. PACAP had no effect on platelet aggregation induced by collagen, ADP or epinephrine. Our results demonstrate that the effects of PACAP on delayed neuronal death may play a significant role in the reduction of the infarct size in vivo, but the antioxidant effect could only be observed at concentrations higher than that used in the model of focal ischemia.