Neuroprotective and immunomodulatory effect of dimethyl-fumarate (DMF) after avulsion and reimplantation of spinal motor roots

Abstract

Central Nervous System (CNS) lesions are of concern regarding the morphological and functional recovery of the patient. Different experimental models of injury have substantiated most of the current knowledge on neuronal regeneration and plasticity and have been instrumental in investigating the potential of different methods and treatments. In this context, avulsion of ventral roots has shown to be a reproducible model, since it results in the degeneration of 80% of axotomized motoneurons between the second and third week after avulsion. However, avulsion-surviving motoneurons have regenerative potential after reimplantation of nerve roots, and may serve as a model of CNS regeneration. In the present study, we will evaluate the immunomodulatory and neuroprotective potential of dimethyl fumarate (DMF), considering its positive effects demonstrated in the treatment of multiple sclerosis, contributing to the future clinical use of motor root implantation. Thus, animals submitted to the avulsion of the spinal motor roots L4 to L6 will be submitted to the acute reimplantation, through the use of heterologous sealant, produced by Centro de Estudos de Venenos de Animais Peçonhentos (CEVAp - Unesp). In sequence, they will be treated with DMF (0, 15, 30 and 45 mg/kg; gavage). The results, after 4 weeks of treatment, will involve analysis of neuronal survival, medullary synaptic preservation, reactive gliosis levels, by using morphological techniques (Nissl staining, Transmission Electron Microscopy and immunohistochemistry) and functional ("walking track test" and von Frey-Electronic). (AU)