Establishment of root reimplantation model after spinal motor roots in C57BL/6J mice: use of fibrin polymer, dimethyl fumarate and swimming

Author(s)

Júlia Lombardi

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2021-10-25

Examining board members

Alexandre Leite Rodrigues de Oliveira; Rogério Martins Amorim; Juliana Carvalho Tavares

• Advisor: Alexandre Leite Rodrigues de Oliveira

Abstract

Brachial and lumbosacral plexus roots injuries result in disconnection between the central and peripheral nervous system, generating paralysis and neuropathic pain. Thus, the prognosis of functional recovery in this type of injury is significantly reduced, since the proximal axotomy results in the death of spinal motoneurons. In order to minimize post-trauma neuronal degeneration, the use of neuroprotective drugs can maximize the potential for recovery, when associated with anatomical restoration of avulsed roots. The present study aimed at establishing a model of ventral root avulsion (VRA) and reimplantation of the lumbosacral roots in mice using a heterologous fibrin biopolymer (BHF). In addition, the association between root replantation with dimethyl fumarate (DMF) and swimming was used to pursue treatment alternatives to optimize neuronal plasticity, synaptic preservation, and motor functionality after injury. For this purpose, female mice of the isogenic C57BL/6J strain were submitted to the surgical procedure of motor roots avulsion (L4-L6) followed or not by reimplantation. The pharmacological treatment was with DMF at a dose of 90mg/kg or methylcellulose (vehicle), and the swimming protocol was created in a way to progressively train the animals, with crescent duration per week and adjustable load to the individual weight. The Walk Track Test was used as a tool in the functional assessment of animals, carried out weekly for the entire experimental protocol. After the established survival time, neuronal survival and immunomodulation were studied by cytochemistry (Nissl staining) and immunofluorescence, respectively. The results, 56 days post-surgery, demonstrate greater neuronal survival for the reimplantation+swimming+DMF (RDNA) and reimplantation+DMF (RD) groups, being 53% and 36%, respectively. These data, associated with the anticipation of the inflammatory cascade and promising functional recovery in the RD group, position DMF as a candidate for the pharmacological approach to neurological injuries. Furthermore, our work is the first to bring not only the model of root replantation with BHF in mice, but to demonstrate the significant neuroptotective capacity of swimming in this type of injury, and the therapeutic potential to be explored as such (AU)

• FAPESP's process: 19/06591-7 - Establishment of a model for spinal root reimplantation after avulsion in C57BL/6J mice: use of fibrin polymer and dimethyl-fumarate
• Grantee: Júlia Lombardi
• Support Opportunities: Scholarships in Brazil - Master