Abstract | BACKGROUND: METHODS: In vitro neuronal culture with oxygen- glucose deprivation and rats with middle cerebral artery occlusion were subjected to DMF/MMF treatment. Live/dead cell counting and LDH assay, as well as behavioral deficits, plasma cytokine assay, western blots, real-time PCR (Q-PCR) and immunofluorescence staining, were used to evaluate the mechanisms and neurological outcomes. RESULTS: We found that MMF significantly rescued cortical neurons from oxygen- glucose deprivation (OGD) in culture and suppressed pro-inflammatory cytokines produced by primary mixed neuron/glia cultures subjected to OGD. In rats, DMF treatment significantly decreased infarction volume by nearly 40 % and significantly improved neurobehavioral deficits after middle cerebral artery occlusion (MCAO). In the acute early phase (72 h after MCAO), DMF induced the expression of transcription factor Nrf2 and its downstream mediator HO-1, important for the protection of infarcted cells against oxidative stress. In addition to its antioxidant role, DMF also acted as a potent immunomodulator, reducing the infiltration of neutrophils and T cells and the number of activated microglia/macrophages in the infarct region by more than 50 % by 7-14 days after MCAO. Concomitantly, the levels of potentially harmful pro-inflammatory cytokines were greatly reduced in the plasma and brain and in OGD neuron/glia cultures. CONCLUSIONS: We conclude that DMF is neuroprotective in experimental stroke because of its potent immunomodulatory and antioxidant effects and thus may be useful as a novel therapeutic agent to treat stroke in patients.
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Authors | Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 13
Issue 1
Pg. 269
(10 13 2016)
ISSN: 1742-2094 [Electronic] England |
PMID | 27733178
(Publication Type: Journal Article)
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Chemical References |
- Inflammation Mediators
- Dimethyl Fumarate
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Topics |
- Animals
- Cells, Cultured
- Dimethyl Fumarate
(pharmacology, therapeutic use)
- Immunity, Cellular
(drug effects, physiology)
- Inflammation Mediators
(antagonists & inhibitors, immunology, metabolism)
- Male
- Neurons
(drug effects, physiology)
- Rats
- Rats, Sprague-Dawley
- Recovery of Function
(drug effects, physiology)
- Stroke
(drug therapy, immunology, metabolism)
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