CNS neuroscience & therapeutics · 2026
Temporal Neuromuscular Adaptations and Proteomic Signatures Following Botulinum Neurotoxin A Injection in Spastic Hemiplegia Rats.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhong Mengru, Lin Huijuan, Yang Xubo, Liu Liru, Xie Yunlan, Peng Tingting, Luo Jie, He Lu, Gao Ting, Tang Hongmei, Xu Kaishou
Аннотация
BACKGROUND: Cerebral palsy (CP) is predominantly characterized by spasticity. While botulinum neurotoxin type A (BoNT-A) effectively reduces spasticity, its transient efficacy represents a major clinical limitation. Elucidating the mechanisms that limit its duration of action may inform strategies to prolong therapeutic benefit.
METHOD: A spastic CP rat model was established via carotid artery ligation and hypoxia in 7-day-old Wistar rats. On postnatal Day 21, BoNT-A (5 U/kg) was administered to the gastrocnemius muscle. Behavioral and molecular biological assessments were performed at 4 and 12 weeks post-injection.
RESULT: At 4 weeks after injection, the motor performance improved, spasticity decreased (p < 0.05), neuromuscular junction density increased, and neurotrophic factors IGF-1, GAP 43, and S100 increased (all p < 0.05). However, these functional and molecular changes diminished by 12 weeks. Further proteomic analysis revealed a shift in pathway enrichment, from protein synthesis and vesicular transport at 4 weeks to metabolic regulation at 12 weeks. Among the differentially expressed proteins, Sar1b and Rtn1, whose expression patterns paralleled with nerve sprouting, may be key regulatory factors.
CONCLUSION: These findings indicate that BoNT-A facilitates NMJ recovery through temporal regulation of energy metabolism, protein synthesis, and vesicular transport. Rtn1 and Sar1b may represent candidate molecular targets for extending the therapeutic effects of BoNT-A, although further functional validation is required.
METHOD: A spastic CP rat model was established via carotid artery ligation and hypoxia in 7-day-old Wistar rats. On postnatal Day 21, BoNT-A (5 U/kg) was administered to the gastrocnemius muscle. Behavioral and molecular biological assessments were performed at 4 and 12 weeks post-injection.
RESULT: At 4 weeks after injection, the motor performance improved, spasticity decreased (p < 0.05), neuromuscular junction density increased, and neurotrophic factors IGF-1, GAP 43, and S100 increased (all p < 0.05). However, these functional and molecular changes diminished by 12 weeks. Further proteomic analysis revealed a shift in pathway enrichment, from protein synthesis and vesicular transport at 4 weeks to metabolic regulation at 12 weeks. Among the differentially expressed proteins, Sar1b and Rtn1, whose expression patterns paralleled with nerve sprouting, may be key regulatory factors.
CONCLUSION: These findings indicate that BoNT-A facilitates NMJ recovery through temporal regulation of energy metabolism, protein synthesis, and vesicular transport. Rtn1 and Sar1b may represent candidate molecular targets for extending the therapeutic effects of BoNT-A, although further functional validation is required.