S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice
BackgroundBrachial plexus root avulsion (BPRA) often occurs in high-speed traffic accidents or shoulder dystocia, resulting in motor dysfunction. S-ketamine, a clinical anesthetic and antidepressant drug, is an NMDA receptor antagonist that may be effective against glutamate excitotoxicity after ner...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1630158/full |
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| author | Ronghua Huang Ronghua Huang Bingbiao Lin Lingtai Yu Lingtai Yu Qichen Luo Hongyan Tian Chenrui Li Naili Wei Shaohui Zhuang Jian Chen Yalan Li Yalan Li |
| author_facet | Ronghua Huang Ronghua Huang Bingbiao Lin Lingtai Yu Lingtai Yu Qichen Luo Hongyan Tian Chenrui Li Naili Wei Shaohui Zhuang Jian Chen Yalan Li Yalan Li |
| author_sort | Ronghua Huang |
| collection | DOAJ |
| description | BackgroundBrachial plexus root avulsion (BPRA) often occurs in high-speed traffic accidents or shoulder dystocia, resulting in motor dysfunction. S-ketamine, a clinical anesthetic and antidepressant drug, is an NMDA receptor antagonist that may be effective against glutamate excitotoxicity after nerve injury. Therefore, we aimed to elucidate the potential effectiveness of S-ketamine on motor function recovery after BPRA in mice.MethodsA mouse model of BPRA and reimplantation was established, and mice were randomly assigned to either the S-ketamine group or the control group, receiving a low, subanesthetic dose of S-ketamine or normal saline, respectively. The restoration of the motor neural circuit—from spinal cord and myocutaneous nerve to biceps muscle—was evaluated. Fluoro-Gold retrograde tracing was utilized to assess the connectivity between the central and peripheral nerve systems. Behavioral tests such as CatWalk, grooming test, and grip strength were applied to assess motor function recovery. The underlying mechanism was analyzed by Western blot, and the rescue experiment was assessed via motor function behavioral tests.ResultsS-ketamine increased motor neuron survival, enhanced central and peripheral nervous connectivity, promoted axon regeneration and remyelination, improved the neuromuscular junction integrity, and prevented muscle atrophy. As a result, motor function recovery was significantly improved, which was attributed to increased BDNF production via ERK-CREB phosphorylation. The BDNF receptor antagonist, ANA12, counteracted the functional recovery induced by S-ketamine.ConclusionS-ketamine increases the BDNF concentration by ERK/CREB phosphorylation, thereby promoting motor neural circuit repair and facilitating motor function recovery. |
| format | Article |
| id | doaj-art-84df28f62f7a437c8a523806329b44b5 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-84df28f62f7a437c8a523806329b44b52025-08-20T03:51:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16301581630158S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in miceRonghua Huang0Ronghua Huang1Bingbiao Lin2Lingtai Yu3Lingtai Yu4Qichen Luo5Hongyan Tian6Chenrui Li7Naili Wei8Shaohui Zhuang9Jian Chen10Yalan Li11Yalan Li12Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, ChinaLaboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Guangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Anesthesiology, Guangzhou Concord Cancer Center, Guangzhou, ChinaBackgroundBrachial plexus root avulsion (BPRA) often occurs in high-speed traffic accidents or shoulder dystocia, resulting in motor dysfunction. S-ketamine, a clinical anesthetic and antidepressant drug, is an NMDA receptor antagonist that may be effective against glutamate excitotoxicity after nerve injury. Therefore, we aimed to elucidate the potential effectiveness of S-ketamine on motor function recovery after BPRA in mice.MethodsA mouse model of BPRA and reimplantation was established, and mice were randomly assigned to either the S-ketamine group or the control group, receiving a low, subanesthetic dose of S-ketamine or normal saline, respectively. The restoration of the motor neural circuit—from spinal cord and myocutaneous nerve to biceps muscle—was evaluated. Fluoro-Gold retrograde tracing was utilized to assess the connectivity between the central and peripheral nerve systems. Behavioral tests such as CatWalk, grooming test, and grip strength were applied to assess motor function recovery. The underlying mechanism was analyzed by Western blot, and the rescue experiment was assessed via motor function behavioral tests.ResultsS-ketamine increased motor neuron survival, enhanced central and peripheral nervous connectivity, promoted axon regeneration and remyelination, improved the neuromuscular junction integrity, and prevented muscle atrophy. As a result, motor function recovery was significantly improved, which was attributed to increased BDNF production via ERK-CREB phosphorylation. The BDNF receptor antagonist, ANA12, counteracted the functional recovery induced by S-ketamine.ConclusionS-ketamine increases the BDNF concentration by ERK/CREB phosphorylation, thereby promoting motor neural circuit repair and facilitating motor function recovery.https://www.frontiersin.org/articles/10.3389/fphar.2025.1630158/fullS-ketaminebrachial plexus root avulsionmotor functionrecoveryBDNF |
| spellingShingle | Ronghua Huang Ronghua Huang Bingbiao Lin Lingtai Yu Lingtai Yu Qichen Luo Hongyan Tian Chenrui Li Naili Wei Shaohui Zhuang Jian Chen Yalan Li Yalan Li S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice Frontiers in Pharmacology S-ketamine brachial plexus root avulsion motor function recovery BDNF |
| title | S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| title_full | S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| title_fullStr | S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| title_full_unstemmed | S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| title_short | S-ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| title_sort | s ketamine facilitates motor function recovery after brachial plexus root avulsion and reimplantation in mice |
| topic | S-ketamine brachial plexus root avulsion motor function recovery BDNF |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1630158/full |
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