Post-Stroke Exercise Enhances Axon Regeneration of Newborn Projection Neurons
Zhang QW, Deng XX, Sun X, Xu JX, Sun FY. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke. PLoS One 2013;8(11):e80139. doi: 10.1371/journal.pone.0080139.
Background: Ischemic stroke often causes degeneration of striatal and cortical neurons and associated motor deficits. Previous studies showed that new neurons generated after stroke can form projections to the substantia nigra, and that physical exercise promotes neurogenesis and functional recovery. However, whether exercise also enhances axon regeneration of newborn projection neurons in the ischemic adult brain remained unclear.
Hypothesis: This study hypothesized that post-stroke treadmill exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons, thereby improving motor function recovery after ischemic injury.
Methods: The authors subjected adult male rats to transient middle cerebral artery occlusion and subsequently provided treadmill exercise for 30 minutes daily from day 5 to day 28 post-stroke. Fluorogold was injected into the substantia nigra to trace projection neurons, and a GFP-retroviral vector was used to label newborn neurons. Immunohistochemistry, confocal microscopy and unbiased stereological cell counting assisted with Stereo Investigator were performed to quantify labeled neurons. Motor recovery was assessed with neurological scoring and rotarod performance.
Results: Exercise significantly improved motor function and increased the numbers of NeuN+, FG+, and GFP+-FG+ neurons in the striatum and cortex ipsilateral to ischemia. It also enhanced tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra, elevated BDNF, VEGF and synapsin expression, and reduced Nogo-A levels.
Conclusions: Post-stroke treadmill exercise promotes axon regeneration of newborn projection neurons and dopaminergic cell survival, enhancing neural repair and motor recovery in ischemic rat brains.
