Electronic Poster | Session 1

039 – Immunomodulation by dimethyl fumarate after ventral root avulsion and reimplantation

Paula Regina Gelinski Kempe (1) – Gabriela Bortolança Chiarotto (1) – Benedito Barraviera (2) – Rui Seabra Ferreira Junior (2) – Alexandre Leite Rodrigues de Oliveira (1)
University of Campinas, Institute of Biology, Campinas, Brazil (1) – Center for the Study of Venoms and Venomous Animals (CEVAP), State University of São Paulo, Botucatu, Brazil (2)

Spinal cord injury causes a critical loss of motor and sensory function. Ventral root avulsion (VRA) is an experimental model in which there is an abrupt separation of the motor roots from the surface of the spinal cord. As a result, most of the axotomized motoneurons degenerate, and a chronic inflammatory state is triggered. It is believed that pharmacological treatment associated with root reimplantation can overcome the degenerative and inflammatory effects of VRA. Therefore, we hypothesize that dimethyl-fumarate (DMF), an FDA approved drug for psoriasis and multiple sclerosis, associated with root repair by using fibrin sealant (FS), a biological glue used for tissue repair, can improve the regenerative response through its immunomodulatory effects, leading to motor function recovery. Thus, adult female Lewis rats (CEUA/UNICAMP: 4500-1; n=75) were subjected to unilateral VRA of L4-L6 roots followed by reimplantation or not and daily treatment with DMF (0 or 15 mg/Kg) for 1 and 12 weeks. The analysis involved neuronal survival (Nissl staining), glial reactivity by immunofluorescence (astrocytes and microglia), gene expression (cytokines, interleukins, and macrophage polarization) and motor function recovery (Catwalk system). Our results indicate that DMF treatment is neuroprotective since it preserved 36% of axotomized motoneurons against only 12% in the control group. Also decreased astrogliosis and microglial reaction and downregulated the pro- inflammatory state. Importantly, the pharmacological treatment was further enhanced when associated with root reimplantation using FS, reaching 70% of motoneuron survival and glial reaction reduced almost by half. Conversely, such protective effects reflected in 50% motor function improvement, showing the efficacy of employing combined regenerative approaches following spinal cord injury.