CILIARY NEUROTROPHIC FACTOR PREVENTS ISCHEMIA-INDUCED LEARNING-DISABILITY AND NEURONAL LOSS IN GERBILS

Ciliary neurotrophic factor (CNTF) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused CNTF continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the region were significantly more numerous in gerbils infused with CNTF than in those receiving vehicle infusion. These findings suggest that CNTF has a trophic effect on ischemic hippocampal neurons.