{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:54:16Z","timestamp":1789116856725,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"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, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2314-B-038-026-MY3 and MOST 108-2321-B-038-008"],"award-info":[{"award-number":["MOST 110-2314-B-038-026-MY3 and MOST 108-2321-B-038-008"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sunny Brain Tumor and Brain Disease Research and Development Fund, Taipei Medical University, Taipei, Taiwan","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"The Intramural Research Program, National Institute on Aging, National Institutes of Health, USA","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"National Institutes of Health R56 AG057028, USA","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Technology development Program of MSS","award":["S2782046"],"award-info":[{"award-number":["S2782046"]}]},{"name":"the National Research Foundation (NRF) grant funded by the Korea government","award":["2021M3A9G2015889"],"award-info":[{"award-number":["2021M3A9G2015889"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6\u2032-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg\/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.<\/jats:p>","DOI":"10.3390\/ijms22158276","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"8276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["3,6\u2032-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Pen-Sen","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-2966","authenticated-orcid":false,"given":"Ping-Yen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Lecca","sequence":"additional","affiliation":[{"name":"Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Luo","sequence":"additional","affiliation":[{"name":"Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Aevis Bio, Inc., Daejeon 34141, Korea"},{"name":"Aevis Bio, Inc., Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Hoffer","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hsiao","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-1468","authenticated-orcid":false,"given":"Nigel H.","family":"Greig","sequence":"additional","affiliation":[{"name":"Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-3351","authenticated-orcid":false,"given":"Jia-Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J. 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