TY  - JOUR
AU  - Bernis, Maria E.
AU  - Hakvoort, Charlotte
AU  - Nacarkucuk, Efe
AU  - Burkard, Hannah
AU  - Bremer, Anna-Sophie
AU  - Zweyer, Margit
AU  - Maes, Elke
AU  - Grzelak, Kora A.
AU  - Sabir, Hemmen
TI  - Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model
JO  - International journal of molecular sciences
VL  - 25
IS  - 15
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DZNE-2024-01008
SP  - 8204
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Oligodendroglia: drug effects
KW  - Oligodendroglia: metabolism
KW  - Neuroprotective Agents: pharmacology
KW  - Neuroprotective Agents: therapeutic use
KW  - Hypoxia-Ischemia, Brain: drug therapy
KW  - Hypoxia-Ischemia, Brain: metabolism
KW  - Hypoxia-Ischemia, Brain: pathology
KW  - Rats
KW  - Clemastine: pharmacology
KW  - MAP Kinase Signaling System: drug effects
KW  - Animals, Newborn
KW  - Disease Models, Animal
KW  - Cell Proliferation: drug effects
KW  - Rats, Sprague-Dawley
LB  - PUB:(DE-HGF)16
C6  - pmid:39125778
C2  - pmc:PMC11311837
DO  - DOI:10.3390/ijms25158204
UR  - https://pub.dzne.de/record/271140
ER  -