INTRAVENTRICULAR ADMINISTRATION OF NITRIC-OXIDE SYNTHASE INHIBITORS PREVENTS DELAYED NEURONAL DEATH IN GERBIL HIPPOCAMPAL CA1 NEURONS

We performed experiments to investigate the participation of nitric oxide (NO) in the delayed neuronal death (DND) of gerbil hippocampal CA1 neurons, following 5-min forebrain ischemia with pretreatment of stereotaxic intraventricular administration of several types of NO synthase inhibitors and biologically inactive control drugs. The number of surviving neurons in the control drug groups administered N-G-monomethyl-D-arginine or N-G-nitro-D-arginine methyl ester was comparable to that in the group administered artificial cerebro-spinal fluid, while the groups administered NOS inhibitors, such as N-G-monomethyl-L-arginine or N-G-nitro-L-arginine methyl ester, showed significant preservation of the neuronal densities compared with the control drug groups, to over 60% of the sham operation group value. Furthermore, intraventricular administration of N-omega-nitro-L-arginine at various concentrations disclosed a dose-dependent protection against the DND. These results suggest that the generation of NO may act to promote the establishment of DND.