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

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.

[The action of amphiphilic drugs on human fibroblasts in vitro. Their possible use in antiviral and antitumor chemotherapy]. / Observations sur l'action de quelques drogues amphiphiles sur les fibroblastes humains in vitro. Applications possibles en chimiothérapie antivirale et antitumorale.

The LDH cytotoxicity test is able to emphasize the stabilisation of human embryo fibroblast membranes, in vitro, by two amphiphilic drugs: the metomidate and the thymolol. The membrane stabilisation is emphasized by the reduced LDH externalization as compared with the untreated cells. The use of the LDH test for the selection of some natural complexes or synthetic drugs with membrane stabilising and potential antiviral activity is proposed. The inhibition of LDH by metomidate was recorded, as decreasing of the enzyme activity with increasing metomidate concentration. This fact explains the known lactic acid accumulation, under metomidate treatment of human subjects. The use of metomidate in classical cancer treatment potentiation is proposed instead of lactate externalization inhibitors, already used for this aim.