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Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model.
Bernis, Maria E; Hakvoort, Charlotte; Nacarkucuk, Efe; Burkard, Hannah; Bremer, Anna-Sophie; Zweyer, Margit; Maes, Elke; Grzelak, Kora A; Sabir, Hemmen.
Afiliación
  • Bernis ME; Neonatologie und Pädiatrische Intensivmedizin, Eltern-Kind-Zentrum, Universitätsklinikum Bonn, 53127 Bonn, Germany.
  • Hakvoort C; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany.
  • Nacarkucuk E; Neonatologie und Pädiatrische Intensivmedizin, Eltern-Kind-Zentrum, Universitätsklinikum Bonn, 53127 Bonn, Germany.
  • Burkard H; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany.
  • Bremer AS; Neonatologie und Pädiatrische Intensivmedizin, Eltern-Kind-Zentrum, Universitätsklinikum Bonn, 53127 Bonn, Germany.
  • Zweyer M; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany.
  • Maes E; Neonatologie und Pädiatrische Intensivmedizin, Eltern-Kind-Zentrum, Universitätsklinikum Bonn, 53127 Bonn, Germany.
  • Grzelak KA; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany.
  • Sabir H; Neonatologie und Pädiatrische Intensivmedizin, Eltern-Kind-Zentrum, Universitätsklinikum Bonn, 53127 Bonn, Germany.
Int J Mol Sci ; 25(15)2024 Jul 27.
Article en En | MEDLINE | ID: mdl-39125778
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligodendroglía / Clemastina / Fármacos Neuroprotectores / Hipoxia-Isquemia Encefálica / Sistema de Señalización de MAP Quinasas / Proliferación Celular / Modelos Animales de Enfermedad / Animales Recién Nacidos Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligodendroglía / Clemastina / Fármacos Neuroprotectores / Hipoxia-Isquemia Encefálica / Sistema de Señalización de MAP Quinasas / Proliferación Celular / Modelos Animales de Enfermedad / Animales Recién Nacidos Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza