Recombinant Human Ciliary Neurotrophic Factor Protects MCAO/R Rat Brain against Neuronal Degeneration and Apoptosis by Regulating NOS Expression

Abstract

To research the effects and mechanisms of recombinant human ciliary neurotrophic factor (rhCNTF) on ischemia/reperfusion in vivo and in vitro, rhCNTF was biosynthesized, and ischemia/reperfusion-like models were used. Protection by rhCNTF was studied at the in vivo level using a model of middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. RhCNTF was administrated just before reperfusion. RhCNTF markedly increased animal viability, decreased infarct volumes and neurological deficit scores. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation/reoxygenation, and treated with rhCNTF prophylactically. Results indicated that neuronal survival rates were increased, LDH release was decreased and lose of neurite length were alleviated in rhCNTF group, and this protection was associated with nerotrophic effect, nitric oxide and neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS). The data suggest that rhCNTF may be a good therapeutic reagent to reduce cerebral ischemia/reperfusion injury, and may act by NOS regulation.