Ischemic Stroke Induces Skeletal Muscle Damage and Alters Transcriptome Profile in Rats

To establish pathological features of skeletal muscle post-stroke and to provide a background for promising interventions. Adult male SD rats were selected and randomly divided into a control group, a sham group, and a middle cerebral artery occlusion (MCAO) group. The tolerance and capability of exercise were separately collected on days 1, 3, 5, and 7 after the MCAO operation. The neurological deficits, brain infarct volume, soleus histopathology, mRNA-seq analysis, flow cytometry, immunofluorescence, and protein expression analysis were performed on the seventh day. Rats in the MCAO group showed that soleus tissue weight, pulling force, exercise capacity, endurance, and muscle structure were significantly decreased. Moreover, the RNA sequencing array revealed that mitochondrial-mediated autophagy was the critical pathological process, and the result of transcriptomic findings was confirmed at the translational level. The mitochondrial membrane potential and the mfn2 and p62 protein expression were decreased, and the Beclin-1, ATG5, Parkin, PINK1, LC3B, and Drp1 expression were upregulated; these results were consistent with immunohistochemistry. This is the first report on the pathological features of limbic symptoms on day 7 after MCAO surgery in rats. In addition, we further confirmed that autophagy is one of the main causative mechanisms of reduced muscle function after stroke.

Automated summary

This study aimed to investigate the pathological features of skeletal muscle post-stroke in rats and to provide background information for potential interventions. The findings showed that decreased spontaneous movement and reduced exercise endurance were the main manifestations of skeletal muscle dysfunction in rats after stroke, which was closely related to mitochondrial-mediated autophagy dysfunction.