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Dimethyl fumarate and monomethyl fumarate promote post-ischemic r | 55673
Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

+44 1478 350008

Dimethyl fumarate and monomethyl fumarate promote post-ischemic recovery in mice


9th Euro-Global Summit on Toxicology and Applied Pharmacology

June 22-24, 2017 Paris, France

Fu-Dong Shi

Tianjin Medical University General Hospital, China
Barrow Neurological Institute, USA

Posters & Accepted Abstracts: J Clin Toxicol

Abstract :

Statement of the Problem: Oxidative stress plays an important role in cerebral ischemia-reperfusion injury. The complexity of the ischemia-reperfusion biological cascade, inadequate dosing of antioxidants and inappropriate targeting by antioxidants are among the possible reasons that have led to the failure of these clinical trials. It remains an urgent need to develop neuroprotective strategies targeting multiple key steps in the biochemical cascade of ischemia-reperfusion injury. Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are antioxidant agents that can activate the nuclear factor erythroid- 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of antioxidant proteins. Methodology & Theoretical Orientation: Transient focal brain ischemia model was used to examine the role of DMF and MMF in the treatment of ischemic stroke in wild type and Nrf2 mutant mice. Neurobehavioral evaluation, MRI, histology, neural cell death, glial activation and expression of genes related to the Nrf2 pathway were analyzed to evaluate whether the Nrf2 pathway mediates the effects in ischemia-reperfusion injury. Findings: In the current study, we demonstrated that DMF and MMF exhibited neuroprotective properties against cerebral ischemia-reperfusion injury with faster and better recovery from initial ischemia-reperfusion. DMF and MMF significantly reduce neurological deficits, infarct volume, brain edema, and cell death. Further, DMF and MMF suppress glial activation following brain ischemia. Importantly, the protection of DMF and MMF was mostly evident during the sub-acute stage and was abolished in Nrf2-/- mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF. Conclusion & Significance: The protection of DMF and MMF was mostly evident during the subacute stage and was abolished in Nrf2-/- mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF.

Biography :

Email: fshi@tmu.edu.cn

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