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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation

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Author(s):
Paula R. G. Kempe [1] ; Gabriela Bortolança Chiarotto [2] ; Benedito Barraviera [3] ; Rui Seabra Ferreira Jr. [4] ; Alexandre L. R. de Oliveira [5]
Total Authors: 5
Affiliation:
[1] University of Campinas. Laboratory of Nerve Regeneration - Brasil
[2] University of Campinas. Laboratory of Nerve Regeneration - Brasil
[3] São Paulo State University. Center for the Study of Venoms and Venomous Animals - Brasil
[4] São Paulo State University. Center for the Study of Venoms and Venomous Animals - Brasil
[5] University of Campinas. Laboratory of Nerve Regeneration - Brasil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 26, 2020-05-20.
Abstract

Abstract Background: Ventral root avulsion (VRA) is an experimental approach 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 by the second week after injury, and the significant loss of synapses and increased glial reaction triggers a chronic inflammatory state. Pharmacological treatment associated with root reimplantation is thought to overcome the degenerative effects of VRA. Therefore, treatment with dimethyl fumarate (DMF), a drug with neuroprotective and immunomodulatory effects, in combination with a heterologous fibrin sealant/biopolymer (FS), a biological glue, may improve the regenerative response. Methods: Adult female Lewis rats were subjected to VRA of L4-L6 roots followed by reimplantation and daily treatment with DMF for four weeks. Survival times were evaluated 1, 4 or 12 weeks after surgery. Neuronal survival assessed by Nissl staining, glial reactivity (anti-GFAP for astrocytes and anti-Iba-1 for microglia) and synapse preservation (anti-VGLUT1 for glutamatergic inputs and anti-GAD65 for GABAergic inputs) evaluated by immunofluorescence, gene expression (pro- and anti-inflammatory molecules) and motor function recovery were measured. Results: Treatment with DMF at a dose of 15 mg/kg was found to be neuroprotective and immunomodulatory because it preserved motoneurons and synapses and decreased astrogliosis and microglial reactions, as well as downregulated the expression of pro-inflammatory gene transcripts. Conclusion: The pharmacological benefit was further enhanced when associated with root reimplantation with FS, in which animals recovered at least 50% of motor function, showing the efficacy of employing multiple regenerative approaches following spinal cord root injury. (AU)

FAPESP's process: 16/25478-9 - Neuroprotective and immunomodulatory effect of dimethyl-fumarate (DMF) after avulsion and reimplantation of spinal motor roots
Grantee:Paula Regina Gelinski Kempe
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/25845-7 - Neuroprotective and immunomodulatory effect of dimethyl-fumarate (DMF) after avulsion and reimplantation of spinal motor roots associated to cell-therapy
Grantee:Paula Regina Gelinski Kempe
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
Grantee:Alexandre Leite Rodrigues de Oliveira
Support type: Research Projects - Thematic Grants