[Effect of naftidrofuryl (LS129) on axonal growth]

The response of growing axons and microtubules to naftidrofuryl (LS 129) was investigated in vitro and in situ in the embryonic nervous system of mice. For this purpose, we used rotatory cultures of post-implanted embryos in a rat or human serum containing the compound combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene-glycol embedded semithin sections. We also analysed the protective effect of naftidrofuryl to treatment with vinka alkaloids using the same method. After culture in rat serum enriched with naftidrofuryl at concentration of 20 microM and above, we observed an increase of both the number of axonal profiles in semithin sections and of the number of microtubules per surface unit in electron micrographs. After culture in human serum obtained from an healthy volunteer after a unique intake of naftidrofuryl at 900 mg/j and above, we observed the same effect of an increasing of the number of axonal profiles in the tectal plate of mice embryos in semithin sections. These results suggest a promoting effect of naftidrofuryl on axonal growth and on microtubules' assembly. They suggest a therapeutic effect of this drug at daily doses of 900 mg/j. After culture in a rat serum enriched with naftidrofuryl at concentration of 20 microM, we observed a protective effect of this drug toward the disruption of axonal microtubules by vinka alkaloids. This effect seems rather specific since we did not observe the same protection toward the mitotic microtubules. These results suggest that naftidrofuryl could be used to prevent the neurological side effects of vinka alkaloids.