PMID- 29199131 OWN - NLM STAT- MEDLINE DCOM- 20181003 LR - 20181004 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 300 DP - 2018 Feb TI - Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia. PG - 222-231 LID - S0014-4886(17)30329-1 [pii] LID - 10.1016/j.expneurol.2017.11.014 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Pak, Malk Eun AU - Pak ME AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Jung, Da Hee AU - Jung DH AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Lee, Hong Ju AU - Lee HJ AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Shin, Myung Jun AU - Shin MJ AD - Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Busan 49241, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea. FAU - Kim, Soo-Yeon AU - Kim SY AD - Department of Rehabilitation Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea. FAU - Shin, Yong Beom AU - Shin YB AD - Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Busan 49241, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea. FAU - Yun, Young Ju AU - Yun YJ AD - Department of Integrative Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Shin, Hwa Kyoung AU - Shin HK AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Choi, Byung Tae AU - Choi BT AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: choibt@pusan.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171202 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 SB - IM MH - Animals MH - Animals, Newborn MH - Cell Proliferation/physiology MH - Combined Modality Therapy/*methods MH - Corpus Callosum/cytology/metabolism/pathology MH - Demyelinating Diseases/metabolism/pathology/*therapy MH - Disease Models, Animal MH - Electroacupuncture/*methods MH - Exercise Test/*methods MH - Female MH - Hypoxia-Ischemia, Brain/metabolism/pathology/*therapy MH - Male MH - Oligodendroglia/*physiology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Electroacupuncture OT - Exercise OT - Neonatal hypoxia-ischemia OT - Oligodendrogenesis EDAT- 2017/12/05 06:00 MHDA- 2018/10/04 06:00 CRDT- 2017/12/05 06:00 PHST- 2017/09/14 00:00 [received] PHST- 2017/11/09 00:00 [revised] PHST- 2017/11/29 00:00 [accepted] PHST- 2017/12/05 06:00 [pubmed] PHST- 2018/10/04 06:00 [medline] PHST- 2017/12/05 06:00 [entrez] AID - S0014-4886(17)30329-1 [pii] AID - 10.1016/j.expneurol.2017.11.014 [doi] PST - ppublish SO - Exp Neurol. 2018 Feb;300:222-231. doi: 10.1016/j.expneurol.2017.11.014. Epub 2017 Dec 2.