Nitric oxide synthase inhibition prevents neuronal death in the developing visual cortex.

During postnatal development of the visual cortex of golden hamster, there is a transient increase in both the expression and the activity of nitric oxide synthase (NOS), which coincides temporally with the formation of ipsilateral retino-collicular and retino-geniculate projections and the functional differentiation of primary visual cortex, suggesting the involvement of NO in the maturation of the visual cortex. In the present study, an inhibitor of NOS, N-nitro-L-arginine (L-NNA) was used to block the NOS activity of newborn golden hamster, and effects on development were examined. L-NNA treatment caused an increase in mortality, and suppression of both body weight gain and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity in the early phase of treatment (before postnatal day 14, PD14). The growth of NADPH-d-positive neurons in the visual cortex was also suppressed by the treatment. In control animals, significant numbers of apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay on PD14, and this apoptosis mainly affected cells in cortical layers II and III. NOS inhibition largely rescued neurons from undergoing apoptosis, indicating that NO may serve as a signal triggering apoptosis and play a role in the maturation of the visual cortex.