Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats

Lin Wu; Shuangxi Chen; Bing He; Guijuan Zhou; Yan Xu; Guanghua Zhu; Juan Xie; Limin Deng; Xuanwei Wen; Sijing Li; Zijian Xiao

doi:10.1186/s12967-023-04399-7

Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats

J Transl Med. 2023 Aug 23;21(1):563. doi: 10.1186/s12967-023-04399-7.

Authors

Lin Wu^#^{1

2

3}, Shuangxi Chen^#^{1

2}, Bing He^{1

2}, Guijuan Zhou^{1

2}, Yan Xu^{1

2}, Guanghua Zhu^{1

2}, Juan Xie^{1

2}, Limin Deng^{1

2}, Xuanwei Wen^{1

2}, Sijing Li^{1

2}, Zijian Xiao^{4

5}

Affiliations

¹ Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, 421001, Hengyang, China.
² Clinical Research Center for Immune-Related Encephalopathy of Hunan Province (The First Affiliated Hospital), Hengyang Medical School, University of South China, Hunan, 421001, Hengyang, China.
³ Department of Neurology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, 421000, Hengyang, People's Republic of China.
⁴ Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, 421001, Hengyang, China. zijian6340@21cn.com.
⁵ Clinical Research Center for Immune-Related Encephalopathy of Hunan Province (The First Affiliated Hospital), Hengyang Medical School, University of South China, Hunan, 421001, Hengyang, China. zijian6340@21cn.com.

^# Contributed equally.

Abstract

Background: Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.

Methods: Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the 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 (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.

Results: NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.

Conclusion: NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.

Keywords: Acetylglutamine (NAG); Brachial plexus root avulsion (BPRA); Inflammation; Motoneuron (MN); Pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atrophy
Brachial Plexus*
Male
Neuralgia* / complications
Rats
Rats, Sprague-Dawley
Spinal Cord