Platelet-derived growth factor prevents ischemia-induced neuronal injuries in vivo

Abstract

Platelet-derived growth factor (PDGF) has been considered to be a neuroprotective factor candidate on the basis of several in vitro studies. However, the in vivo effect of PDGF on ischemic neurons has not been determined. In the present study, the effect of PDGF-BB on the ischemia-induced disability of passive avoidance task and hippocampal CA1 neuron death in normothermic gerbils, whose brain temperature was kept at 37.0±0.2°C during 3-min occlusion of the common carotid arteries was investigated. When PDGF-BB was continuously infused for 7 days into the cerebral ventricles of gerbils with transient forebrain ischemia, response latency time in a passive avoidance task was significantly prolonged. Subsequent histological examinations showed that PDGF-BB effectively increased the number of viable pyramidal neurons in the hippocampal CA1 region as well as synapses within the strata moleculare, radiatum and oriens of the region in comparison with the numbers of neurons and synapses in vehicle-treated ischemic gerbils. In situ detection of DNA fragmentation (TUNEL staining) revealed that TUNEL-positive neurons in the hippocampal CA1 field of vehicle-treated ischemic gerbils were much more numerous than those in the field of PDGF-BB-treated ischemic animals after 7 days ischemia. These findings suggest that the present ischemic animal model exhibits a more delayed neuronal degeneration of the hippocampal CA1 field than the conventional 5-min ischemic model and that the 7-day infusion of PDGF-BB, starting 2 h before ischemic insult, not only prevents delayed neuronal death in the hippocampal CA1 field at 7 days after forebrain ischemia but also inhibits a slowly progressive neuronal degeneration occurring thereafter.