Present address: MR-Center, LBK, NTNU, Postboks 8905, N-7491 Trondheim, Norway.
Doxycycline treatment in a neonatal rat model of hypoxia–ischemia reduces cerebral tissue and white matter injury: a longitudinal magnetic resonance imaging study
Article first published online: 17 MAY 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 36, Issue 1, pages 2006–2016, July 2012
How to Cite
Widerøe, M., Havnes, M. B., Morken, T. S., Skranes, J., Goa, P.-E. and Brubakk, A.-M. (2012), Doxycycline treatment in a neonatal rat model of hypoxia–ischemia reduces cerebral tissue and white matter injury: a longitudinal magnetic resonance imaging study. European Journal of Neuroscience, 36: 2006–2016. doi: 10.1111/j.1460-9568.2012.08114.x
- Issue published online: 2 JUL 2012
- Article first published online: 17 MAY 2012
- Received 7 November 2011, revised 10 February 2012, accepted 9 March 2012
- brain injury;
- diffusion tensor imaging;
- manganese-enhanced magnetic resonance imaging;
Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic–ischemic brain injury through its anti-inflammatory effects. The aim of this study was to examine any long-term neuroprotection by doxycycline treatment on cerebral gray and white matter. Hypoxic–ischemic brain injury was induced in 7-day-old rats. Pups were treated with either doxycycline (HI+doxy) or saline (HI+vehicle) by intraperitoneal injection at 1 h after hypoxia–ischemia (HI). At 6 h after HI, MnCl2 was injected intraperitoneally for later manganese-enhanced magnetic resonance imaging (MRI). MRI was performed with diffusion-weighted imaging on day 1 and T1-weighted imaging and diffusion tensor imaging at 7, 21 and 42 days after HI. Animals were killed after MRI on day 42 and histological examinations of the brains were performed. There was a tendency towards lower lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1 day after HI. Volumetric MRI showed increasing differences between groups with time after HI, with less cyst formation and less cerebral tissue loss among HI+doxy than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after HI, indicating reduced inflammation. HI+doxy pups had higher fractional anisotropy on diffusion tensor imaging in major white matter tracts in the injured hemisphere than HI+vehicle pups, indicating less injury to white matter and better myelination. Histological examinations supported the MRI results. Lesion size on early MRI was highly correlated with final injury measures. In conclusion, a single dose of doxycycline reduced long-term cerebral tissue loss and white matter injury after neonatal HI, with an increasing effect of treatment with time after injury.