{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:15:57Z","timestamp":1791389757725,"version":"4.3.3"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bill and Melinda Gates Foundation","award":["INV-002321"],"award-info":[{"award-number":["INV-002321"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neonatal hypoxic-ischemic encephalopathy is the most common cause of long-term disability in term neonates, and white matter injury is the primary cause of cerebral palsy. Therapies that focus on the neuroprotection of myelination and oligodendrocyte proliferation could potentially ameliorate long-lasting neurological impairments after hypoxic-ischemic encephalopathy. Clemastine, a histamine H1 antagonist, has been shown to exert neuroprotective effects in multiple sclerosis and spinal cord injury by promoting oligodendrogenesis and re-myelination. In this study, we demonstrated the neuroprotective effects of clemastine in our rat model of neonatal hypoxic-ischemic brain injury. Animals received a single intraperitoneal injection of either vehicle or clemastine (10 mg\/kg) for 6 consecutive days. Our results showed a significant reduction in white matter loss after treatment, with a clear effect of clemastine on oligodendrocytes, showing a significant increase in the number of Olig2+ cells. We characterized the MAPK\/ERK pathway as a potential mechanistic pathway underlying the neuroprotective effects of clemastine. Altogether, our results demonstrate that clemastine is a potential compound for the treatment of hypoxic-ischemic encephalopathy, with a clear neuroprotective effect on white matter injury by promoting oligodendrogenesis.<\/jats:p>","DOI":"10.3390\/ijms25158204","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:37:25Z","timestamp":1722332245000},"page":"8204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK\/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Maria E.","family":"Bernis","sequence":"first","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Hakvoort","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1605-4868","authenticated-orcid":false,"given":"Efe","family":"Nacarkucuk","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Burkard","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Sophie","family":"Bremer","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-1869","authenticated-orcid":false,"given":"Margit","family":"Zweyer","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Maes","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kora A.","family":"Grzelak","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemmen","family":"Sabir","sequence":"additional","affiliation":[{"name":"Neonatologie und P\u00e4diatrische Intensivmedizin, Eltern-Kind-Zentrum, Universit\u00e4tsklinikum Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S2352-4642(21)00311-4","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201319: An updated systematic analysis with implications for the Sustainable Development Goals","volume":"6","author":"Perin","year":"2022","journal-title":"Lancet Child Adolesc. 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