H.B.S. and C.J.E. contributed equally to this work.
Effect of minocycline on inflammation-induced damage to the blood–brain barrier and white matter during development
Article first published online: 10 DEC 2007
European Journal of Neuroscience
Volume 26, Issue 12, pages 3465–3474, December 2007
How to Cite
Stolp, H. B., Ek, C. J., Johansson, P. A., Dziegielewska, K. M., Potter, A. M., Habgood, M. D. and Saunders, N. R. (2007), Effect of minocycline on inflammation-induced damage to the blood–brain barrier and white matter during development. European Journal of Neuroscience, 26: 3465–3474. doi: 10.1111/j.1460-9568.2007.05973.x
- Issue published online: 10 DEC 2007
- Article first published online: 10 DEC 2007
- Received 12 July 2007, revised 8 October 2007, accepted 1 November 2007
- blood–brain barrier;
- white matter
Damage to white matter in some premature infants exposed to intrauterine infections is thought to involve disruption of the blood–brain barrier. We have examined the effect of minocycline, an agent reported to reduce brain damage resulting from inflammation, on inflammation-induced disruption of the blood–brain barrier and damage to white matter. Post-natal marsupial opossums (Monodelphis domestica) were studied as most brain development in this species occurs after birth. Single intraperitoneal lipopolysaccharide (LPS) injection (0.2 mg/kg) with or without minocycline (45 mg/kg) at post-natal day (P)35 caused short-lasting barrier breakdown to plasma proteins but not to 14C-sucrose. By P44, blood–brain barrier integrity was intact but a reduced volume of white matter was present. At P44 after prolonged inflammation (5 × 0.2 mg/kg LPS at 48 h intervals), proteins from blood were observed within brain white matter and permeability to 14C-sucrose in the hindbrain increased by 31%. The volume of the external capsule and the proportion of myelin were 70 and 57%, respectively, of those in control animals. Minocycline administered during prolonged inflammation restored blood–brain barrier integrity but not LPS-induced damage to white matter. These data suggest that long-term changes in blood–brain barrier permeability occur only after a prolonged period of inflammation during development; however, damage to white matter can result from even a short-lasting breakdown of the barrier. Manipulation of the inflammatory response may have implications for prevention of some developmentally induced neurological conditions.