{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:52:01Z","timestamp":1788918721333,"version":"build-2803163510"},"reference-count":96,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["107-2320-B-415-006"],"award-info":[{"award-number":["107-2320-B-415-006"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["108-2320-B-003- 006-MY3"],"award-info":[{"award-number":["108-2320-B-003- 006-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-65-46006"],"award-info":[{"award-number":["20-65-46006"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among the global youth and commonly results in long-lasting sequelae, including paralysis, epilepsy, and a host of mental disorders such as major depressive disorder. Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&amp;E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent for preventing the long-term adverse effect of mTBI-J.<\/jats:p>","DOI":"10.3390\/pharmaceutics13122169","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"2169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age"],"prefix":"10.3390","volume":"13","author":[{"given":"Shih-Te","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-8277","authenticated-orcid":false,"given":"Hsiu-Yi","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Sun","family":"Ro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung University College of Medicine, Taipei 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-4267","authenticated-orcid":false,"given":"Ming-Feng","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"},{"name":"Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung University College of Medicine, Taipei 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara G.","family":"Amstislavskaya","sequence":"additional","affiliation":[{"name":"Institute of Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4265-8981","authenticated-orcid":false,"given":"Maria A.","family":"Tikhonova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Models of Neurodegenerative Processes, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600355, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Tung","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1007\/s00415-019-09541-4","article-title":"Recent advances in traumatic brain injury","volume":"266","author":"Khellaf","year":"2019","journal-title":"J. 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