Thèse soutenue

Neuropathie diabétique/ischémique et rôle d'un inhibiteur de la sémaphorine 3A dans la régénération axonale/vasculaire
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Auteur / Autrice : Pierre Lozeron
Direction : Bernard Lévy
Type : Thèse de doctorat
Discipline(s) : Biothérapies et biotechnologies
Date : Soutenance en 2014
Etablissement(s) : Paris 7

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Résumé

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As a chronic disease diabetes is susceptible to induce macro and microangiopathic complications. They are evidences from epidemiological and histological studies in man and experimental studies in animal to suspect a close correlation between macrovascular disease and peripheral neuropathy. We developed an animal model of diabetic neuropathy by multiple injections of streptozotocine (60mg/kg) in C57B16 mice. Alter lé weeks of hyperglycaemia, diabetic neuropathy was identified by reduction of motor and sensory nerve conduction velocities. To enhance ischemic involvement we performed a permanent ligature of the right femoral artery. We characterised the behavioural, vascular (large and small vessels) and nervous involvement (large and small fibres) in this model. Semaphorin3A is involved in nervous system development. It reduces endothelial cells migration and axonal growth. We evaluated the semaphorin3A and its receptors Neuropilin-1 and Plexin-Al in our diabetic ischemic neuropathy model. Sema3A is transiently increased at D4 post ischemia in the muscle and at D7 in the nerve. During the treatment with an antagonist of semaphorin3A (SM¬345431), our first results indicate a beneficial effect of the treatment of vascular function while nervous function remained unchanged or deteriorated. These preliminary results need to be substantiate by on-going and future experiments