Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens.

Michelle Carty, Julie Wixey, Colditz, Paul B. and Buller, Kathryn M. (2008) Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens.. International Journal of Developmental Neuroscience, 26 5: 477-485. doi:10.1016/j.ijdevneu.2008.02.005


Author Michelle Carty
Julie Wixey
Colditz, Paul B.
Buller, Kathryn M.
Title Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens.
Journal name International Journal of Developmental Neuroscience   Check publisher's open access policy
ISSN 1873-474X
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.ijdevneu.2008.02.005
Open Access Status
Volume 26
Issue 5
Start page 477
End page 485
Total pages 8
Editor Perez-Polo, J.
Place of publication UK
Publisher Pergamon
Language eng
Subject 920111 Nervous System and Disorders
110903 Central Nervous System
C1
Abstract An increase in the number of activated microglia in the brain is a key feature of neuroinflammation after a hypoxic-ischemic insult to the preterm neonate and can contribute to white matter injury in the brain. Minocycline is a potent inhibitor of microglia and may have a role as a neuroprotective agent that ameliorates brain injury after hypoxia-ischemia in neonatal animal models. However to date large doses, pre-insult administration and short periods of treatment after hypoxia-ischemia have mostly been investigated in animal models making it difficult to translate minocycline's potential applicability to protect the human preterm neonatal brain exposed to hypoxia-ischemia. We investigated whether repeated doses of minocycline can minimize white matter injury and neuroinflammation one week after hypoxia-ischemia (right carotid artery ligation and 30 min 6% O(2)) in the post-natal day 3 rat pup. Two dosage regimens of minocycline were administered for one week; a high dose of 45 mg/kg 2 h after hypoxia-ischemia then 22.5 mg/kg daily or a low dose 22.5 mg/kg 2 h after hypoxia-ischemia then 10 mg/kg. Post-natal day 3 hypoxia-ischemia significantly reduced myelin content, numbers of O1- and O4-positive oligodendrocyte progenitor cells and increased activated microglia one week later on post-natal day 10. The low dose minocycline regimen was as effective as the high dose in ameliorating neuroinflammation after post-natal day 3 hypoxia-ischemia. However only the high dose regimen significantly attenuated reductions in O1- and O4-positive oligodendrocyte progenitor cells and myelin content. The low dose only significantly attenuated the reduction in O1-positive oligodendrocyte cell counts. Repeated, daily, post-insult treatment with minocycline abolished neuroinflammation and may provide neuroprotection to white matter for up to one week after hypoxia-ischemia in a rodent preterm, model. The present findings suggest the potential clinical relevance of a repeated, daily minocycline treatment strategy, administered after a hypoxia-ischemia insult, as a therapeutic intervention for hypoxia-ischemia-affected preterm neonates. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved.
Keyword Developmental Biology
Neurosciences
Developmental Biology
Neurosciences & Neurology
DEVELOPMENTAL BIOLOGY
NEUROSCIENCES
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
UQ Centre for Clinical Research Publications
 
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Created: Mon, 30 Mar 2009, 00:50:38 EST by Amanda Barnett on behalf of UQ Centre for Clinical Research