Neuroprotective effects of pre-ischemic exercise are linked to expression of NT-3/NT-4 and TrkB/TrkC in rats

Stroke causes irreversible damage, particularly to the hippocampus. Evidence suggests that exercise training may mitigate adverse structural and functional consequences of an ischemic lesion in the brain. The purpose of this study was to investigate the effects of preconditioning exercise on expression of neurotrophic factor genes and proteins in hippocampalCA1 region and their relationship with sensorimotor recovery following global ischemia/reperfusion (Is/Re) injury in a rat model of stroke.

Male Wistar rats were randomly assigned to Exercise+Ischemia/Reperfusion (Ex+Is/Re),Control+Ischemia/Reperfusion (Co+Is/Re), and Sham treatments. Rats in the exercise groups ran on a treadmill for 45 min/d for five days/week for 8 consecutive weeks prior to Is/Re lesion.Ischemia was induced by common carotid artery occlusion (CCAO). The ladder rung walking task was used to assess functional impairments and recovery following ischemic lesion.Tissue from hippocampal area CA1 was inspected for ischemia-induced cell loss and gene and protein expression linked to neurotrophins NT-3, NT-4, and their receptorsTrkB and TrkC.

CCAO caused hippocampal cell death in CA1 and resulted in significant sensori motor impairments in the ladder rung walking task. In contrast, pre-ischemic exercise considerably reduced cell death and supported sensorimotor recovery following CCAO.In addition, NT-3, NT-4,TrkB and TrkC gene expression and their protein levels were significantly increased inthe Ex+Is/Re group compared to Co+Is/Re (p < 0.05).

The findings showed that pre-ischemic exercise can exert neuroprotective effects via NT-3 and NT-4 pathways against ischemia in hippocampal CA1 neurons and promote post-injury sensorimotor recovery.