Neurological research · 2026
Inhibition of RGMa attenuates neuronal autophagy and improves neurological function in a rat ischemia/reperfusion model.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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.
Xie Fei, Liang Hanxi, Li Xia, Li Jun, Qin Xinyue
Аннотация
BACKGROUND: Ischemic stroke (IS) is a leading global cause of morbidity and mortality, with neuronal autophagy playing a pivotal role in ischemia/reperfusion (I/R) injury following stroke. Repulsive guidance molecule A (RGMa), known for its involvement in axon guidance and neuronal repair, has recently been linked to I/R injury. This study aimed to explore RGMa's role in neuronal autophagy and its therapeutic potential in mitigating I/R-induced damage using a rat model.
METHODS: A middle cerebral artery occlusion (MCAO) model was used in 108 male Sprague-Dawley rats, divided into six groups (n = 18 each): sham, I/R, I/R+NS, I/R + 6FNIII (RGMa antagonist), I/R+rAd-HK (empty vector), and I/R+rAd-shRGMa (RGMa-silencing adenovirus). RGMa was inhibited via stereotaxic injections of 6FNIII or rAd-shRGMa. Infarct volume (n = 3), neurological deficits (n = 5), and autophagy (n = 3-4) were evaluated using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, behavioral scores, immunofluorescence, Western blotting, and transmission electron microscopy (TEM). RGMa's autophagy mechanism was assessed by co-immunoprecipitation.
RESULTS: RGMa inhibition with 6FNIII or rAd-shRGMa significantly reduced infarct volume (n = 3, p < 0.05) and neurological deficits (n = 5, p < 0.05) 24 hours post-I/R compared to I/R, I/R+NS, and I/R+rAd-HK groups. Autophagy marker LC3II/I decreased (n = 4, p < 0.01), and autophagosome formation was reduced (n = 3) in treated groups. RGMa did not interact with Beclin1-PIK3C3, suggesting a Beclin1-independent pathway.
METHODS: A middle cerebral artery occlusion (MCAO) model was used in 108 male Sprague-Dawley rats, divided into six groups (n = 18 each): sham, I/R, I/R+NS, I/R + 6FNIII (RGMa antagonist), I/R+rAd-HK (empty vector), and I/R+rAd-shRGMa (RGMa-silencing adenovirus). RGMa was inhibited via stereotaxic injections of 6FNIII or rAd-shRGMa. Infarct volume (n = 3), neurological deficits (n = 5), and autophagy (n = 3-4) were evaluated using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, behavioral scores, immunofluorescence, Western blotting, and transmission electron microscopy (TEM). RGMa's autophagy mechanism was assessed by co-immunoprecipitation.
RESULTS: RGMa inhibition with 6FNIII or rAd-shRGMa significantly reduced infarct volume (n = 3, p < 0.05) and neurological deficits (n = 5, p < 0.05) 24 hours post-I/R compared to I/R, I/R+NS, and I/R+rAd-HK groups. Autophagy marker LC3II/I decreased (n = 4, p < 0.01), and autophagosome formation was reduced (n = 3) in treated groups. RGMa did not interact with Beclin1-PIK3C3, suggesting a Beclin1-independent pathway.