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Myelination inducti...
Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury.
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Rangon, Claire-Marie (author)
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Schang, Anne-Laure (author)
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Van Steenwinckel, Juliette (author)
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Schwendimann, Leslie (author)
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Lebon, Sophie (author)
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Fu, Tingting (author)
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Chen, Libo (author)
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Beneton, Veronique (author)
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Journiac, Nathalie (author)
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Young-Ten, Pierrette (author)
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Bourgeois, Thomas (author)
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Maze, Johanna (author)
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Matrot, Boris (author)
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Baburamani, Ana A (author)
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Supramaniam, Veena (author)
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- Mallard, Carina, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Trottet, Lionel (author)
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Edwards, A David (author)
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- Hagberg, Henrik, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Fleiss, Bobbi (author)
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Li, Jingjun (author)
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Chuang, Tsu Tshen (author)
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Gressens, Pierre (author)
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: Brain, behavior, and immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 74, s. 265-276
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- 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 preterm birth itself and predictor of the severity of WMI is exposure to maternal-fetal infection-inflammation such as chorioamnionitis. There are no neurotherapeutics for this WMI. To affect this healthcare need, the repurposing of drugs with efficacy in other white matter injury models is an attractive strategy. As such, we tested the efficacy of GSK247246, an H3R antagonist/inverse agonist, in a model of inflammation-mediated WMI of the preterm born infant recapitulating the main clinical hallmarks of human brain injury, which are oligodendrocyte maturation arrest, microglial reactivity, and hypomyelination. WMI is induced by mimicking the effects of maternal-fetal infection-inflammation and setting up neuroinflammation. We induce this process at the time in the mouse when brain development is equivalent to the human third trimester; postnatal day (P)1 through to P5 with i.p. interleukin-1β (IL-1β) injections. We initiated GSK247246 treatment (i.p at 7mg/kg or 20mg/kg) after neuroinflammation was well established (on P6) and it was administered twice daily through to P10. Outcomes were assessed at P10 and P30 with gene and protein analysis. A low dose of GSK247246 (7mg/kg) lead to a recovery in protein expression of markers of myelin (density of Myelin Basic Protein, MBP & Proteolipid Proteins, PLP) and a reduction in macro- and microgliosis (density of ionising adaptor protein, IBA1 & glial fibrillary acid protein, GFAP). Our results confirm the neurotherapeutic efficacy of targeting the H3R for WMI seen in a cuprizone model of multiple sclerosis and a recently reported clinical trial in relapsing-remitting multiple sclerosis patients. Further work is needed to develop a slow release strategy for this agent and test its efficacy in large animal models of preterm infant WMI.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Rangon, Claire-M ...
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Schang, Anne-Lau ...
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Van Steenwinckel ...
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Schwendimann, Le ...
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Lebon, Sophie
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Fu, Tingting
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show more...
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Chen, Libo
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Beneton, Veroniq ...
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Journiac, Nathal ...
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Young-Ten, Pierr ...
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Bourgeois, Thoma ...
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Maze, Johanna
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Matrot, Boris
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Baburamani, Ana ...
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Supramaniam, Vee ...
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Mallard, Carina, ...
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Trottet, Lionel
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Edwards, A David
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Hagberg, Henrik, ...
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Fleiss, Bobbi
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Li, Jingjun
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Chuang, Tsu Tshe ...
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Gressens, Pierre
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Brain, behavior, ...
- By the university
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University of Gothenburg