Acetylglutamine facilitates motor recovery after brachial plexus root avulsion in ratsby promoting motoneuronal survival and axonal remyelination

Background: Brachial plexus root avulsion (BPRA) is a disabling peripheral nerve injury that induces substantial death of motoneurons, degeneration of motor axons and de-innervation of biceps muscles, leading toloss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proved to exert neuroprotective and anti-inflammatory effects in various disorders in the nervous system. Hence, the present study focused on the effect of NAG on motor recovery after BPRA in rats and the underlying mechanisms. Methods: : Adult male Sprague Dawley rats were subject to BPRA and reimplantation surgery andsubsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR was utilized to measure the mRNA levels of remyelination and regenerstion indicators on myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the anterior horn of the spinal cord were measured using Western blot analysis. Results: : Our results indicated NAG could significantly accelerate recovery of motor function in the injured forelimbs, enhance motoneuronal survival in the anterior horn of the spinal cord, inhibit the expression of proinflammatory cytokines and pyroptosis pathway, facilitate axonal remyelination in the myocutaneous nerve and alleviate atrophy of biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA. Conclusion: NAG promotes functional motor recovery by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for NAG to be a novel strategy for BPRA treatment.