Neuronal nitric oxide synthase inhibitor attenuates number of regenerating motoneurons after peripheral nerve implantation following spinal root avulsion in adult rats

Abstract

Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to citrulline and nitric oxide (NO). The expression of this enzyme is associated with both physiology and pathophysiology conditions, depending on cell types and expression level. In spinal motoneurons, it is de novo synthesized after ventral root avulsion. Potential roles of NOS expression on motoneuron survival were extensively studied whereas effects of NOS in neuronal regeneration are under-explored. In this study, a peripheral nerve was implanted to the cervical segment where the ventral roots were avulsed in adult SD rats. Isoform specific NOS inhibitor was soaked in gel foam and topically applied on the lesioned site. After 2, 4 and 8 weeks, the rats were sacrificed and spinal cords were harvested. Samples were and cut into 40 micrometer thick sections and examined under microscope. Majority of the cells survived after nerve implantation as compared to 50% cell lose in control group without implantation at 4 weeks. The number of regenerating motoneurons was halved in inhibitor- treated group compared to control (96 vs 204 cells) whereas the speed of axonal regeneration showed no difference as revealed by double retrograde labelings. The results showed that inhibiting NOS could attenuate the number of regenerating motoneurons and suggested that NOS might contribute to the axonal regeneration of motoneuron after a peripheral nerve implantation. It supports the beneficial role of the expression of NOS after avulsion in rat.