{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:53:44Z","timestamp":1775883224643,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Convergence of Conventional Medicine and Traditional Korean Medicine R&amp;D project funded by the Ministry of Health &amp; Welfare through the Korea Health Industry Development Institute","award":["HI14C0704"],"award-info":[{"award-number":["HI14C0704"]}]},{"name":"the National Research Foundation of Korea, funded by the Korean government","award":["2014R1A5A2009936"],"award-info":[{"award-number":["2014R1A5A2009936"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4\u20136 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose.<\/jats:p>","DOI":"10.3390\/life10100240","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T08:59:22Z","timestamp":1602665962000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Electroacupuncture on the Scalp over the Motor Cortex Ameliorates Behavioral Deficits Following Neonatal Hypoxia-Ischemia in Rats via the Activation of Neural Stem Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Da Hee","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"},{"name":"Graduate Training Program of Korean Medicine for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malk Eun","family":"Pak","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"},{"name":"Graduate Training Program of Korean Medicine for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"},{"name":"Graduate Training Program of Korean Medicine for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Min","family":"Ahn","sequence":"additional","affiliation":[{"name":"Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Gyeongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ju","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Il","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University, Yangsan 50612, Gyeongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwa Kyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"},{"name":"Graduate Training Program of Korean Medicine for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea"},{"name":"Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Gyeongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-1204","authenticated-orcid":false,"given":"Seo-Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wonkwang University School of Medicine, Iksan 54538, Jeonbuk, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-4346","authenticated-orcid":false,"given":"Byung Tae","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Korea"},{"name":"Graduate Training Program of Korean Medicine for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea"},{"name":"Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Gyeongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0140-6736(05)71048-5","article-title":"Lancet Neonatal Survival Steering, T. 4 million neonatal deaths: When? Where? Why?","volume":"365","author":"Lawn","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fncel.2017.00078","article-title":"Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges","volume":"11","author":"Millar","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1542\/peds.2006-2839","article-title":"Determinants of outcomes after head cooling for neonatal encephalopathy","volume":"119","author":"Wyatt","year":"2007","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1523\/JNEUROSCI.0477-04.2004","article-title":"Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: A protective role for topiramate","volume":"24","author":"Follett","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/jcbfm.2014.41","article-title":"Mechanisms of perinatal arterial ischemic stroke","volume":"34","author":"Natarajan","year":"2014","journal-title":"J. Cereb Blood Flow Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejogrb.2008.01.003","article-title":"Factors associated with umbilical artery acidemia in term infants with low Apgar scores at 5 min","volume":"139","author":"Locatelli","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.brainres.2005.03.013","article-title":"Erythropoietin prevents long-term sensorimotor deficits and brain injury following neonatal hypoxia-ischemia in rats","volume":"1045","author":"Spandou","year":"2005","journal-title":"Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.pedhc.2006.06.007","article-title":"Cerebral palsy: Introduction and diagnosis (part I)","volume":"21","author":"Jones","year":"2007","journal-title":"J. Pediatr. Health Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1161\/STROKEAHA.113.002813","article-title":"Oxidative stress interferes with white matter renewal after prolonged cerebral hypoperfusion in mice","volume":"44","author":"Miyamoto","year":"2013","journal-title":"Stroke"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1161\/STROKEAHA.110.599654","article-title":"Stem cell research in stroke: How far from the clinic?","volume":"42","author":"Lindvall","year":"2011","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/jcbfm.2011.187","article-title":"Stem cell therapy for cerebral ischemia: From basic science to clinical applications","volume":"32","author":"Abe","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nm747","article-title":"Neuronal replacement from endogenous precursors in the adult brain after stroke","volume":"8","author":"Arvidsson","year":"2002","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xu, M.M., Li, D., and Zhang, S.H. (2018). Acupuncture for acute stroke. Cochrane Db Syst. Rev.","DOI":"10.1002\/14651858.CD003317.pub3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.expneurol.2017.11.014","article-title":"Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia","volume":"300","author":"Pak","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, Y.R., Kim, H.N., Ahn, S.M., Choi, Y.H., Shin, H.K., and Choi, B.T. (2014). Electroacupuncture promotes post-stroke functional recovery via enhancing endogenous neurogenesis in mouse focal cerebral ischemia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090000"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.3892\/ijmm.2015.2334","article-title":"Electro-acupuncture exerts beneficial effects against cerebral ischemia and promotes the proliferation of neural progenitor cells in the cortical peri-infarct area through the Wnt\/beta-catenin signaling pathway","volume":"36","author":"Chen","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28646","DOI":"10.1038\/srep28646","article-title":"Electroacupuncture ameliorates memory impairments by enhancing oligodendrocyte regeneration in a mouse model of prolonged cerebral hypoperfusion","volume":"6","author":"Ahn","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","first-page":"8638294","article-title":"Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats","volume":"2018","author":"Kim","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"480950","DOI":"10.1155\/2012\/480950","article-title":"Scalp acupuncture for acute ischemic stroke: A meta-analysis of randomized controlled trials","volume":"2012","author":"Wang","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1186\/s13063-016-1611-y","article-title":"Scalp acupuncture and electromagnetic convergence stimulation for patients with cerebral infarction: Study protocol for a randomized controlled trial","volume":"17","author":"Han","year":"2016","journal-title":"Trials"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pelletier, S.J., and Cicchetti, F. (2014). Cellular and molecular mechanisms of action of transcranial direct current stimulation: Evidence from in vitro and in vivo models. Int. J. Neuropsychopharmacol., 18.","DOI":"10.1093\/ijnp\/pyu047"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"608496","DOI":"10.1155\/2011\/608496","article-title":"CNPase expression in olfactory ensheathing cells","volume":"2011","author":"Radtke","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_24","first-page":"389","article-title":"Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow Mononuclear Cell Transplantation","volume":"17","author":"Sharma","year":"2015","journal-title":"Cell. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.spen.2004.01.006","article-title":"Animal models of hypoxic-ischemic brain damage in the newborn","volume":"11","author":"Yager","year":"2004","journal-title":"Semin Pediatr. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1542\/peds.2008-2816","article-title":"Meta-analysis of neurobehavioral outcomes in very preterm and\/or very low birth weight children","volume":"124","author":"Oosterlaan","year":"2009","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1242\/dmm.002915","article-title":"Towards improved animal models of neonatal white matter injury associated with cerebral palsy","volume":"3","author":"Silbereis","year":"2010","journal-title":"Dis. Model. Mech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/nn.3263","article-title":"Impaired adult myelination in the prefrontal cortex of socially isolated mice","volume":"15","author":"Liu","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11884","DOI":"10.1523\/JNEUROSCI.1220-14.2014","article-title":"TACE\/ADAM17 is essential for oligodendrocyte development and CNS myelination","volume":"34","author":"Palazuelos","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/NEN.0b013e3182496429","article-title":"Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants","volume":"71","author":"Verney","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature09614","article-title":"Myelination and support of axonal integrity by glia","volume":"468","author":"Nave","year":"2010","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neuroimage.2005.01.019","article-title":"DTI tractography based parcellation of white matter: Application to the mid-sagittal morphology of corpus callosum","volume":"26","author":"Huang","year":"2005","journal-title":"Neuroimage"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.nicl.2017.05.005","article-title":"White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function","volume":"15","author":"Pannek","year":"2017","journal-title":"Neuroimage Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1126\/science.1254446","article-title":"Neuroscience. A new wrap for neuronal activity?","volume":"344","author":"Bechler","year":"2014","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1252304","DOI":"10.1126\/science.1252304","article-title":"Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain","volume":"344","author":"Gibson","year":"2014","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7907","DOI":"10.1523\/JNEUROSCI.1299-06.2006","article-title":"Origin of oligodendrocytes in the subventricular zone of the adult brain","volume":"26","author":"Menn","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1126\/science.287.5457.1433","article-title":"Mammalian neural stem cells","volume":"287","author":"Gage","year":"2000","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1089\/scd.2006.15.407","article-title":"Identification of astrocyte-expressed factors that modulate neural stem\/progenitor cell differentiation","volume":"15","author":"Barkho","year":"2006","journal-title":"Stem Cells Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.5607\/en.2016.25.3.103","article-title":"Adult Neurogenesis and Gliogenesis: Possible Mechanisms for Neurorestoration","volume":"25","author":"Rusznak","year":"2016","journal-title":"Exp. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1038\/srep03981","article-title":"A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke","volume":"4","author":"Wang","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.3892\/ijmm.2013.1511","article-title":"Effects of electroacupuncture on apoptotic pathways in a rat model of focal cerebral ischemia","volume":"32","author":"Kim","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_42","first-page":"613","article-title":"Electroacupuncture Promotes Remyelination after Cuprizone Treatment by Enhancing Myelin Debris Clearance","volume":"10","author":"Zhu","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.expneurol.2016.02.018","article-title":"Transcranial direct current stimulation accelerates recovery of function, induces neurogenesis and recruits oligodendrocyte precursors in a rat model of stroke","volume":"279","author":"Braun","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1634\/stemcells.2007-1022","article-title":"Direct-current electrical field guides neuronal stem\/progenitor cell migration","volume":"26","author":"Li","year":"2008","journal-title":"Stem Cells"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.expneurol.2014.09.014","article-title":"Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt\/GSK3beta signaling","volume":"263","author":"Liu","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1007\/s10439-014-1058-9","article-title":"Short duration electrical stimulation to enhance neurite outgrowth and maturation of adult neural stem progenitor cells","volume":"42","author":"Kobelt","year":"2014","journal-title":"Ann. Biomed. Eng."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2715196","DOI":"10.1155\/2016\/2715196","article-title":"Transcranial Direct Current Stimulation Modulates Neurogenesis and Microglia Activation in the Mouse Brain","volume":"2016","author":"Pikhovych","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1093\/brain\/awf238","article-title":"Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability","volume":"125","author":"Liebetanz","year":"2002","journal-title":"Brain"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bcp.2017.04.029","article-title":"Modulation of neurogenesis via neurotrophic factors in acupuncture treatments for neurological diseases","volume":"141","author":"Shin","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fneur.2016.00094","article-title":"Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation","volume":"7","author":"Alam","year":"2016","journal-title":"Front. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1038\/s41598-018-20481-3","article-title":"Potential benefits of mesenchymal stem cells and electroacupuncture on the trophic factors associated with neurogenesis in mice with ischemic stroke","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/10\/10\/240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:21:13Z","timestamp":1760178073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/10\/10\/240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,14]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["life10100240"],"URL":"https:\/\/doi.org\/10.3390\/life10100240","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,14]]}}}