Apport d'un modèle murin de neuropathie démyélinisante inflammatoire au développement de thérapeutiques : caractérisations fonctionnelle et morphologique

Abstract

To finalize a mouse model of inflammatory demyelinating neuropathy, we injected a solution containing a bovine pancreas protease, active at neutral pH, in the perineural space of the mouse left sciatic nerve (a nerve consisting of myelinated axons). The locomotive behaviour of animals was daily followed and, between 3 and 45 days after the injection, the sciatic nerves were removed from animals, studied using classical electrophysiological techniques and then, at least for some of them, examined using conventional microscopy. The right sciatic nerve, which did not receive a perineural injection, is a very good control, because it comes from the same animal as the left sciatic nerve which underwent the injection. The results obtained show that, under our experimental conditions, i) a demyelinisation of nerve fibres can be detected between 6 and 15 days after the injection of protease, resulting in a defective axonal conduction of action potentials, and ii) 45 days are sufficient to restore a normal axonal conduction. These results are interesting since they indicate that this mouse model can be used to test the ability of new pharmaceutical agents to counteract the defective nerve conduction of action potentials arising after an axonal demyelinisation, in the perspective of developing new useful molecules for the treatment of inflammatory demyelinating neuropathies.