Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hippocampal CA I field of the gerbil brain

Fibroblast growth factors (FGFs) are polypeptides with various biological a ctivities in vivo and in vitro, and their receptors are expressed in the wi despread and specific neuronal populations of the brain. In this study, we asked whether keratinocyte growth factor (KGF), one of the FGF superfamily, would express in the brain, and have neuroprotective against ischemic brai n injury. In situ hybridization analysis revealed that intense silver grain s for KGF mRNA are observed in the neuronal cells of the cerebral cortex, h ippocampus and amygdala in gerbil brain. Continuous cerebroventricular infu sion of KGF (20 mug) for a 7 day period to gerbils starting 2 days before t emporary right carotid artery occlusion (20 min) resulted in a higher survi val rate than seen in vehicle-treated ischemic animals. Subsequent histolog ical examinations showed that KGF effectively prevented delayed neuronal de ath of the hippocampal CAI region. In situ detection of DNA fragmentation ( TUNEL staining) revealed that ischemic animals infused with KGF contained f ewer TUNEL-positive neurons in the hippocampal CAI field than those infused with vehicle alone at the forth and seventh day after ischemia. KGF-treate d brain showed over-expression of KGF mRNA in the neuronal cells of the cer ebral cortex, hippocampus only in the right hemisphere, which was the side of carotid artery occlusion, 8-10 h after ischemia. These findings suggest that KGF has a protective effect against ischemic hippocampal neuronal dama ge in vivo, which may provide a new therapeutic strategy in the survival an d reconstruction of neurons in response to cerebral injury. NeuroReport 12: 71-76 (C) 2001 Lippincott Williams & Wilkins.