Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia

• Published in: Experimental neurology 2018-02, Vol.300, p.222-231
• Main Authors: Pak, Malk Eun, Jung, Da Hee, Lee, Hong Ju, Shin, Myung Jun, Kim, Soo-Yeon, Shin, Yong Beom, Yun, Young Ju, Shin, Hwa Kyoung, Choi, Byung Tae
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Brain-derived neurotrophic factor; Cell Proliferation - physiology; Combined Modality Therapy - methods; Corpus Callosum - cytology; Corpus Callosum - metabolism; Corpus Callosum - pathology; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelinating Diseases - therapy; Disease Models, Animal; Electroacupuncture; Electroacupuncture - methods; Exercise; Exercise Test - methods; Female; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - therapy; Male; Neonatal hypoxia-ischemia; Oligodendrogenesis; Oligodendroglia - physiology; Pregnancy; Rats; Rats, Sprague-Dawley
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2017.11.014

We investigated whether electroacupuncture (EA) and treadmill (TM) exercise improve behaviors related to motor and memory dysfunction in a cerebral palsy-like rat model via activation of oligodendrogenesis. A neonatal hypoxia-ischemia model was created using Sprague-Dawley rats (P7), and these underwent EA stimulation and treadmill training from 3 to 5weeks after hypoxia-ischemia induction. EA treatment was delivered via electrical stimulation (2Hz, 1mA) at two acupoints, Baihui (GV20) and Zusanli (ST36). Behavioral tests showed that EA alleviated motor dysfunction caused by hypoxia-ischemia on a rotarod test, and TM exercise alleviated motor and memory dysfunction seen on cylinder and passive avoidance tests. Combined therapy with EA and TM exercise showed synergistic effects on the cylinder, rotarod, and catwalk tests. TM exercise significantly restored corpus callosum thickness, and combined therapy with EA and TM restored myelin basic protein (MBP) levels in this region. While EA stimulation only increased activation of cAMP-response element binging protein (CREB) in oligodendrocytes of the corpus callosum, TM exercise increased newly generated oligodendrocyte progenitor cells or oligodendrocytes via activation of CREB. Synergistic effects on oligodendrogenesis were also observed by the combined therapy. Furthermore, the combined therapy induced mature brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex. These results demonstrate that combined therapy with EA and TM exercise may restore myelin components following neonatal hypoxia-ischemia via upregulation of oligodendrogenesis involving CREB/BDNF signaling, which subsequently improves motor and memory function. Therefore, combined therapy with EA and TM exercise offers another treatment option for functional recovery from injuries caused by neonatal hypoxia-ischemia, such as cerebral palsy. [Display omitted] •EA and TM combined therapy alleviated hypoxia–ischemia-induced motor dysfunction.•Combined therapy restored myelin components in the corpus callosum.•Combined therapy enhanced oligodendrogenesis via CREB activation.•Combined therapy induced mature BDNF expression in the cerebral cortex.