Comparative analysis of the beneficial effects of treadmill training and electroacupuncture in a rat model of neonatal hypoxia-ischemia

In the present study, we investigated whether treadmill training and electroacupuncture (EA) have autonomous or synergistic beneficial effects on deficits caused by neonatal hypoxia-ischemia in Sprague-Dawley rats. For this purpose, rats subjected to hypoxia-ischemia underwent treadmill training and EA stimulation from 4 to 8 weeks of age. Conventional EA (CEA) and scalp EA (SEA) were delivered by electrical stimulation (2 Hz, 1 mA) at traditional acupoints and at the scalp to the primary motor area, respectively. In the behavioral examination, markedly improved performances in the rotarod test were observed in the rats that underwent treadmill exercise, and in the rats that underwent treadmill exercise and CEA compared to the untreated rats subjected to hypoxia-ischemia. An improvement was also observed in the passive avoidance test in the rats that underwent treadmill training and EA. As shown by western blot analysis, the expression levels of neuronal nuclei (NeuN), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase and myelin basic protein (MBP) exhibited a significant decrease in the contralateral subventricular zone (SVZ) of the rats subjected to hypoxia-ischemia compared to the controls; however, these expression levels increased following treadmill exercise and EA stimulation. As shown by immunohistochemical analyses, the thickness of the corpus callosum and the integrated optical density (IOD) of MBP were significantly increased in the rats subjected to treadmill exercise and EA compared to the untreated rats subjected to hypoxiaa-ischemia. The synergistic effects of treadmill training and EA were also observed in the protein levels and IOD of MBP. A marked increase in the number of bromodeoxyuridine (BrdU)- and BrdU/NeuN-positive cells in the contralateral SVZ was also observed in the rats that underwent treadmill training and EA; the number of BrdU-positive cells was synergistically affected by treadmill training and EA. These results suggest that treadmill training and EA stimulation contribute to the enhancement of behavioral recovery following hypoxia-ischemia via the upregulation of myelin components and neurogenesis. Thus, treatment with EA stimulation, as well as treadmill training offers another treatment option to promote functional recovery in cerebral palsy.