Very early treadmill exercise facilitates neuroprotection and functional recovery following cerebral ischemia in rats

Exercise is an effective strategy for stroke treatment. However, the time-dependent effects of exercise initiation and the involved mechanisms are controversial. We investigated the effects of very early treadmill exercise on motor functional, cell death and expression of neurotrophin3 (NT3), neurotrophin4 (NT4) and receptors TrkB and TrkC in the hippocampal CA1 region. Twenty-four adult male Wistar rats were subjected to transient Global cerebral ischemia by Common carotid artery occlusion model (CCAo) and were randomly assigned to Sham group, non-exercise group and Very Early exercise group. Rats in the exercise group, received treadmill training initiated at 24 h after operation (for 45 min for 5days/week for 8 consecutive weeks). The Brain cells death were detected by cresyl violet (Nissl) and hematoxylin and eosin (H&E) staining and also motor function by ladder rung walking test. Real-time PCR assessed NT3, NT4 and TrkB and TrkC gene expression in CA1 and associated protein expression was identified using immunohistochemistry. The results showed that very early exercise significantly decreased cell death and increased the gene and protein expression of NT3, NT4, TrkB, and TrkC compared with the non-exercise group (p < 0.05). These changes were consistent with reduced cell death and improved motor function. These results suggested that very early exercise could provide neuroprotection at least in part, through upregulation of neurotrophic factors and their receptors and inhibition of neuronal cell death.