title: Inhibition of nitric oxide synthase promotes facial axonal regeneration  following neurorrhaphy.
abstract: Reconnection of interrupted peripheral nerve by microsurgical suture is a common clinical practice. However, the extent to which peripheral neurorrhaphy improves nerve regeneration and functional recovery remains unsatisfactory. Here, we used anatomical and electrophysiological techniques to investigate the temporal correlation between the expressions of oxidative stress-related biomarkers such as neuronal nitric oxide synthase (nNOS) and the facial axonal regeneration after an immediate facial nerve repair in adult rats since peripheral nerve lesion is well known to induce a dramatic increase of NOS expression in the affected neuronal cell bodies. We found that compared to nerve cut without suture, facial nerve repair not only caused the facial axonal regeneration but also consistently prevented the fluctuations of expressions of oxidative stress-related biomarkers in 10 weeks postlesion. To further elucidate the role of nitric oxide (NO) in the axonal degeneration/regeneration, four different NOS inhibitors were applied to additional rats after facial nerve cut or repair. Both of facial nerve cut+NOS inhibition and facial nerve repair+NOS inhibition were seen to prevent the alterations of expressions of the biomarkers, no matter which NOS inhibitor was used. Moreover, we found that facial nerve repair+NOS inhibition promoted earlier and better axonal regeneration than facial nerve repair, demonstrated by labeling of neuromuscular junctions, retrograde tracing, and electromyography. These results provide direct evidence that peripheral nerve suture and/or treatment of NOS inhibitors can maintain the homeostasis of oxidative stress-related biomarkers, especially nNOS in neuronal cell bodies. These actions may thus facilitate the axonal regeneration.
authors.affiliation: Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan.
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Wang
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Tsai
authors.forename: Jiun-Jen
authors.initials: JJ
authors.lastname: Huang
authors.forename: Hsuan-Chi
authors.initials: HC
authors.lastname: Huang
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Lin
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Liu