Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia.
OBJECTIVE
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.
Lechpammer
M
M
Department of Neurology, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Manning
S M
SM
Samonte
F
F
Nelligan
J
J
Sabo
E
E
Talos
D M
DM
Volpe
J J
JJ
Jensen
F E
FE
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D004195:Disease Models, Animal; D006801:Humans; D002534:Hypoxia, Brain / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D008911:Minocycline / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013681:Tegmentum Mesencephali / Q000293:injuries* / Q000473:pathology
D004676:Myelin Basic Protein; D008911:Minocycline