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Study about the neuroprotection efficiency of immunomodulation drugs in mice with experimental autoimmune encephalomyelitis (EAE) previously submitted to a preconditioning protocol by physical exercise

Grant number: 15/04665-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2018
Field of knowledge:Biological Sciences - Morphology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Alexandre Leite Rodrigues de Oliveira
Grantee:Danielle Bernardes
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Background: Studies with multiple sclerosis (MS) as well as its animal model, experimental autoimmune encephalomyelitis (EAE), suggest anti-inflammatory-independent neuroprotective role of the immunomodulation drugs glatiramer acetate (GA), interferon (IFN)-² and dimethyl fumarate (DMF). However, as the results demonstrate partial clinical efficacy, it has been also suggested that a late rescue of the neural damage is not possible, signaling to the importance of the association of neuroprotective strategies to these approaches. In this regard, preconditioning (PC) protocols aim to the development of an adaptive response of the central nervous system (CNS) in favor of neuroprotective mechanisms while regular physical activity has been described as one of the safer and less harmful methods currently employed to do so. Aim: To investigate the effects of the association between PC by physical exercise and pharmacological treatment by immunomodulators (AG, IFN-² and DMF) in the progression of dendritic, synaptic and axonal damages in EAE animals. Methods: Half of the animals addressed to this study will be randomly assigned to a PC protocol by daily exercise and, after 4 weeks, all animals will be induced to the EAE model. In the first clinical remission, the animals will receive standard doses of the above immunomodulators in different experiments. The disease progression will be systematically studied by assessments of clinical presentation, in vivo imaging, histopathological and immunohistochemical studies and gene expression. Expected results: the association between PC and immunomodulators might provide new tools for the understanding of their roles in neuroprotection as well as the molecular mechanisms underlying the neural damage in EAE and possibly MS (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BERNARDES, DANIELLE; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Regular Exercise Modifies Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis. FRONTIERS IN NEUROLOGY, v. 9, NOV 20 2018. Web of Science Citations: 2.
BERNARDES, DANIELLE; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Comprehensive catwalk gait analysis in a chronic model of multiple sclerosis subjected to treadmill exercise training. BMC Neurology, v. 17, AUG 22 2017. Web of Science Citations: 5.
FRERIA, C. M.; BERNARDES, D.; ALMEIDA, G. L.; SIMOES, G. F.; BARBOSA, G. O.; OLIVEIRA, A. L. R. Impairment of toll-like receptors 2 and 4 leads to compensatory mechanisms after sciatic nerve axotomy. JOURNAL OF NEUROINFLAMMATION, v. 13, MAY 24 2016. Web of Science Citations: 13.

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