Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotonergic system in the immature rat brain

Wixey, J. A., Reinebrant, H. E., Spencer, S. J. and Buller, K. M. (2011) Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotonergic system in the immature rat brain. Neuroscience, 182 184-192. doi:10.1016/j.neuroscience.2011.03.033


Author Wixey, J. A.
Reinebrant, H. E.
Spencer, S. J.
Buller, K. M.
Title Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotonergic system in the immature rat brain
Journal name Neuroscience   Check publisher's open access policy
ISSN 0306-4522
1873-7544
Publication date 2011-05-19
Sub-type Article (original research)
DOI 10.1016/j.neuroscience.2011.03.033
Volume 182
Start page 184
End page 192
Total pages 9
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon
Collection year 2012
Language eng
Abstract Neuroinflammation is a key mechanism contributing to long-term neuropathology observed after neonatal hypoxia-ischemia (HI). Minocycline, a second-generation tetracycline, is a potent inhibitor of neuroinflammatory mediators and is successful for at least short-term amelioration of neuronal injury after neonatal HI. However the long-term efficacy of minocycline to prevent injury to a specific neuronal network, such as the serotonergic (5-hydroxytryptamine, 5-HT) system, is not known. In a post-natal day 3 (P3) rat model of preterm HI we found significant reductions in 5-HT levels, 5-HT transporter expression and numbers of 5-HT-positive dorsal raphé neurons 6 weeks after insult compared to control animals. Numbers of activated microglia were significantly elevated in the thalamus and dorsal raphé although the greatest numbers were observed in the thalamus. Brain levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also significantly elevated on P45 in the thalamus and frontal cortex. Post-insult administration of minocycline for 1 week (P3-P9) attenuated the P3 HI-induced increases in numbers of activated microglia and levels of TNF-α and IL-1β on P45 with concurrent changes in serotonergic outcomes. The parallel prevention of P3 HI-induced serotonergic changes suggests that inhibition of neuroinflammation within the first week after P3 HI injury was sufficient to prevent long-term neuroinflammation as well as serotonergic system damage still evident at 6 weeks. Thus early, post-insult administration of minocycline may target secondary neuroinflammation and represent a long-term therapy to preserve the integrity of the central serotonergic network in the preterm neonate. © 2011 IBRO.
Keyword Hypoxia-ischemia
Minocycline
Neonate
Neuroinflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under Neurodegeneration, Neuroprotection, and Disease-Oriented Neuroscience

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2012 Collection
School of Medicine Publications
 
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Created: Wed, 15 Jun 2011, 11:23:25 EST by Dr Kathryn Buller on behalf of UQ Centre for Clinical Research