Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury.

摘要: Fifteen million babies are born preterm every year and a significant number suffer from permanent neurological injuries linked to white matter injury (WMI). A chief cause of birth itself predictor the severity WMI is exposure maternal-fetal infection-inflammation such as chorioamnionitis. There no neurotherapeutics for this WMI. To affect healthcare need, repurposing drugs with efficacy in other models an attractive strategy. As such, we tested GSK247246, H3R antagonist/inverse agonist, model inflammation-mediated infant recapitulating main clinical hallmarks human brain injury, which oligodendrocyte maturation arrest, microglial reactivity, hypomyelination. induced by mimicking effects setting up neuroinflammation. We induce process at time mouse when development equivalent third trimester; postnatal day (P)1 through P5 i.p. interleukin-1β (IL-1β) injections. initiated GSK247246 treatment (i.p 7 mg/kg or 20 mg/kg) after neuroinflammation was well established (on P6) it administered twice daily P10. Outcomes were assessed P10 P30 gene protein analysis. low dose (7 mg/kg) lead recovery expression markers myelin (density Myelin Basic Protein, MBP & Proteolipid Proteins, PLP) reduction macro- microgliosis ionising adaptor protein, IBA1 glial fibrillary acid GFAP). Our results confirm neurotherapeutic targeting seen cuprizone multiple sclerosis recently reported trial relapsing-remitting patients. Further work needed develop slow release strategy agent test its large animal