Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia

Mirna Lechpammer, S. M. Manning, F. Samonte, J. Nelligan, E. Sabot, D. M. Talos, J. J. Volpet, F. E. Jensent

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Aims: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. Methods: In this study, we examine the time course of CD-68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post-insult treatment. Results: We show that preoligodendrocyte injury in the post-natal day 6 begins within 24 h and continues for 48-96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD-68+ microglial cell numbers. Conclusions: These results suggest that anti-inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post-insult treatment strategy.

Original languageEnglish (US)
Pages (from-to)179-193
Number of pages15
JournalNeuropathology and Applied Neurobiology
Volume34
Issue number4
DOIs
StatePublished - Aug 2008
Externally publishedYes

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Periventricular Leukomalacia
Minocycline
Rodentia
Ischemia
Wounds and Injuries
Therapeutics
Premature Infants
Cell Death
Anti-Inflammatory Agents
Cell Count
White Matter
Hypoxia
Infection

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neurology
  • Histology
  • Physiology (medical)

Cite this

Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia. / Lechpammer, Mirna; Manning, S. M.; Samonte, F.; Nelligan, J.; Sabot, E.; Talos, D. M.; Volpet, J. J.; Jensent, F. E.

In: Neuropathology and Applied Neurobiology, Vol. 34, No. 4, 08.2008, p. 179-193.

Research output: Contribution to journalArticle

Lechpammer, Mirna ; Manning, S. M. ; Samonte, F. ; Nelligan, J. ; Sabot, E. ; Talos, D. M. ; Volpet, J. J. ; Jensent, F. E. / Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia. In: Neuropathology and Applied Neurobiology. 2008 ; Vol. 34, No. 4. pp. 179-193.
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