Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice

Background: Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in sp...

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Main Authors: Mengting Zhang, Li Chen, Heren Gao, Tao Liu
Format: Article
Language:English
Published: IMR Press 2025-05-01
Series:Journal of Integrative Neuroscience
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Online Access:https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37357
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author Mengting Zhang
Li Chen
Heren Gao
Tao Liu
author_facet Mengting Zhang
Li Chen
Heren Gao
Tao Liu
author_sort Mengting Zhang
collection DOAJ
description Background: Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation. Methods: We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy. Results: LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI. Conclusion: LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.
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spelling doaj-art-2b5463f76c394e1a9b04b3c2d700e5a62025-08-20T03:25:59ZengIMR PressJournal of Integrative Neuroscience0219-63522025-05-012453735710.31083/JIN37357S0219-6352(25)00929-5Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in MiceMengting Zhang0Li Chen1Heren Gao2Tao Liu3College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, ChinaDepartment of neurology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 201306 Shanghai, ChinaCollege of Acupuncture and Massage, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, ChinaOrthopedic Center, Maanshan General Hospital of Ranger-Duree Healthcare, 243000 Maanshan, Anhui, ChinaBackground: Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation. Methods: We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy. Results: LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI. Conclusion: LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37357lamotrigineautophagyspinal cord injuriesapoptosisneuroprotection
spellingShingle Mengting Zhang
Li Chen
Heren Gao
Tao Liu
Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
Journal of Integrative Neuroscience
lamotrigine
autophagy
spinal cord injuries
apoptosis
neuroprotection
title Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
title_full Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
title_fullStr Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
title_full_unstemmed Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
title_short Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice
title_sort lamotrigine enhances autophagy and reduces post traumatic spinal neural injury in mice
topic lamotrigine
autophagy
spinal cord injuries
apoptosis
neuroprotection
url https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37357
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AT lichen lamotrigineenhancesautophagyandreducesposttraumaticspinalneuralinjuryinmice
AT herengao lamotrigineenhancesautophagyandreducesposttraumaticspinalneuralinjuryinmice
AT taoliu lamotrigineenhancesautophagyandreducesposttraumaticspinalneuralinjuryinmice