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

Ciliary neurotrophic factor (CNTF) has been shown to have potent neuro trophic activity on peripheral and central neurons in vitro and in viv o. However, it remains to be determined whether or not CNTF rescues hi ppocampal CA1 neurons from lethal ischemia and prevents ischemia-induc ed 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 occur rence of ischemia-induced learning disability in a dose-dependent mann er as revealed by the step-down passive avoidance task. Subsequent lig ht and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the s trata moleculare, lacunosum/radiatum and oriens of the region were sig nificantly more numerous in gerbils infused with CNTF than in those re ceiving vehicle infusion. These findings suggest that CNTF has a troph ic effect on ischemic hippocampal neurons.