Establishment of a model for spinal root reimplantation after avulsion in C57BL/6J mice: use of fibrin polymer and dimethyl-fumarate

Abstract

Brachial and lumbosacral plexus lesions result in disconnection between the central and peripheral nervous system, generating paralysis and neuropathic pain. The proximity of the injury to the spinal cord leads to motoneurons death, significantly reducing the prognosis of functional recovery. In order to minimize posttraumatic neuronal degeneration, the use of neuroprotective drugs may maximize recovery potential when associated with the anatomical restoration of the avulsed roots. The present study will associate dimethyl fumarate (DMF) and avulsed nerve root reimplantation as treatment, aiming to optimize neuronal plasticity, synaptic maintenance and motor installation after injury. To that end, 75 female mice of the isogenic strain C57BL/6J will undergo the surgical procedure of motor root avulsion (L4-L6) followed by reimplantation with a fibrin sealant (SF) application. The groups are divided into three experimental groups: G1 = Avulsion + vehicle, G2 = Avulsion + reimplantation with SF, and G3 = Avulsion + reimplantation with SF + DMF (90mg/kg). Treatment with DMF will be avaluated at the 4 and 8 week post-surgical times. Neuronal survival, synaptic changes and immunomodulation will be studied by cytochemistry (Nissl staining), immunohistochemistry and RT-PCR, respectively. The functional recovery will be evaluated by the track test, using a CatWalk (Noldus) platform. (AU)