Abstract
Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO) can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function. Exercise training post-stroke improves motor recovery in clinic patients and increases striatal neurogenesis in experimental animals. This study aimed to investigate the effects of exercise on axon regeneration of newborn projection neurons in adult rat brains following ischemic stroke. Rats were subjected to a transient MCAO to induce focal cerebral ischemic injury, followed by 30 minutes of exercise training daily from 5 to 28 days after MCAO. Motor function was tested using the rotarod test. We used fluorogold (FG) nigral injection to trace striatonigral and corticonigral projection neurons, and green fluorescent protein (GFP)-targeting retroviral vectors combined with FG double labeling (GFP+ -FG+) to detect newborn projection neurons. The results showed that exercise improved the recovery of motor function of rats after MCAO. Meanwhile, exercise also increased the levels of BDNF and VEGF, and reduced Nogo-A in ischemic brain. On this condition, we further found that exercise significantly increased the number of GFP+ -FG+ neurons in the striatum and frontal and parietal cortex ipsilateral to MCAO, suggesting an increase of newborn striatonigral and corticonigral projection neurons by exercise post-stroke. In addition, we found that exercise also increased NeuN+ and FG+ cells in the striatum and frontal and parietal cortex, the ischemic territory, and tyrosine hydroxylase (TH) immunopositive staining cells in the substantia nigra, a region remote from the ischemic territory. Our results provide the first evidence that exercise can effectively enhance the capacity for regeneration of newborn projection neurons in ischemic injured mammalian brains while improving motor function. Our results provide a very important cellular mechanism to illustrate the effectiveness of rehabilitative treatment post-stroke in the clinic.
Highlights
Stroke is the leading cause of disability and the third highest cause of death in the world [1]
We found that the treadmill training in rats with ischemic stroke significantly increased the numbers of newborn striatonigral and corticonigral projection neurons and improved motor function recovery
Recovery in Rats after Transient Cerebral Ischemia First, we investigated whether our exercise protocols (Fig. 1A)
Summary
Stroke is the leading cause of disability and the third highest cause of death in the world [1]. Many surviving stroke patients show morphological brain damage accompanied by neuronal function deficits in the acute phase. Some patients recover after long-term rehabilitative treatment. Many studies have focused on understanding the mechanism of rehabilitative treatment for stroke patients in recent years [2,3]. Previous studies have demonstrated that treadmill training can significantly reduce brain infarct volume and improve neurological outcomes after focal cerebral ischemia [4]. The exact molecular and cellular mechanisms are still unclear
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