Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats

Rehabilitation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intensities, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3β signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 People’s Hospital, China.