{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:20:13Z","timestamp":1791840013583,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174522"],"award-info":[{"award-number":["82174522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305428"],"award-info":[{"award-number":["82305428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebral palsy (CP) is a neurodevelopmental disorder that has been linked to gut microbiota dysbiosis. Although Tuina has shown neuroprotective effects, it remains unclear whether these benefits involve regulation of the gut\u2013brain axis. This study aimed to evaluate the therapeutic effects of Tuina in CP rats, with emphasis on its potential regulation of the gut\u2013brain axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CP was induced in 7\u2010day\u2010old Sprague\u2013Dawley rats through hypoxia\u2013ischemia. Beginning on postnatal day 8 (P8), the Tuina group received daily Tuina therapy for 32 consecutive days. Motor function was assessed using the negative geotaxis test (P6\u2013P12), the beam balance test (P36\u2013P39), and the modified neurological severity score on P40. Gut microbiota composition was analyzed\u00a0using 16S rRNA sequencing. Brain and intestinal histopathology were evaluated histologically via hematoxylin\u2013eosin and Luxol fast blue staining. Protein expression of BDNF, Nrf2, GPX4, ZO\u20101, and occludin was assessed via western blotting and immunofluorescence. Serum short\u2010chain fatty acids (SCFAs) were measured by mass spectrometry, whereas oxidative stress and intestinal barrier markers (superoxide dismutase, malondialdehyde, glutathione peroxidase, lipopolysaccharide [LPS], diamine oxidase [DAO], and D\u2010lactate [D\u2010LA]) were detected using enzyme\u2010linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In CP models induced by hypoxic\u2013ischemic encephalopathy, significant brain injury and motor dysfunction were observed, accompanied by gut microbiota dysbiosis and impaired intestinal barrier function. Tuina intervention improved motor function and growth, regulated gut microbiota, and increased serum SCFA levels. It also enhanced intestinal barrier proteins (occludin, ZO\u20101), reduced serum levels of LPS, DAO, and D\u2010LA, and increased the expression of brain\u2010derived BDNF, Nrf2, and GPX4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tuina significantly alleviated brain injury and improved motor function in CP rats. These effects were associated with modulation of the gut microbiota and restoration of intestinal barrier integrity, suggesting that the gut\u2013brain axis may mediate the neuroprotective effects of Tuina.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71136","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:37:56Z","timestamp":1765978676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neuroprotective Effects of Tuina in CP Rats Are Associated With Gut Microbiota Remodeling and Intestinal Barrier Restoration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3036-0440","authenticated-orcid":false,"given":"Chenqin","family":"Si","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-6503","authenticated-orcid":false,"given":"Rui","family":"Qiao","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1312-9354","authenticated-orcid":false,"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-3011","authenticated-orcid":false,"given":"Ayipaxiaguli","family":"Kasimu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-9922","authenticated-orcid":false,"given":"Danmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0328-6820","authenticated-orcid":false,"given":"Lijian","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8446-5598","authenticated-orcid":false,"given":"Ping\u2010ping","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Science Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-9396","authenticated-orcid":false,"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University  Shanghai China"},{"name":"Department of Pediatrics Jinshan Hospital Affiliated to Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12071314"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02449"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101802"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2025.104421"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp-23-566"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15071620"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-024-01494-1"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25137379"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2017.11.006"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12040657"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.993146"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.09.013"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00394"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03504-2"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1518-1"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/wjtcm.wjtcm_101_24"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1067367"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aninu.2021.09.012"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1782157"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.enzmictec.2021.109836"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-025-00624-0"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijfoodmicro.2016.10.019"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1028909"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2022.111572"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e3181870ba7"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1109469"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3791\/65625"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.11.007"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgad427"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-311012"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1225875"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.10.006"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020318"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.976239"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1147718"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwad026"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2015-001184"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2024.09.002"},{"key":"e_1_2_13_40_1","first-page":"377","article-title":"[Effect of Electroacupuncture on Mood and Estrogen Receptor \u03b1 Expression in Mice With Polycystic Ovary Syndrome Induced by Bisphenol A Exposure]","volume":"47","author":"Xu C.\u2010X.","year":"2022","journal-title":"Zhen ci yan jiu = Acupuncture Research"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-025-01105-1"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1195382"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.656"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000023469"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1282085"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71136","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.71136","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:43:20Z","timestamp":1789980200000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.71136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/brb3.71136"],"URL":"https:\/\/doi.org\/10.1002\/brb3.71136","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71136"}}