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Updated: May 21, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Inhibition of RGMa attenuates neuronal autophagy and improves neurological function in a rat ischemia/reperfusion
Fei Xie1,2, Hanxi Liang1, Xia Li3
1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
