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- Clausen, Bettina Hjelm, et al.
(författare)
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Fumarate decreases edema volume and improves functional outcome after experimental stroke
- 2017
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 295, s. 144-154
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Tidskriftsartikel (refereegranskat)abstract
- Background Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl-fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after ischemic stroke in mice. Methods Permanent middle cerebral artery occlusion (pMCAO) was performed using adult, male C57BL/6 mice. Thirty minutes after pMCAO, 20 mg/kg MMF was administered intravenously. Outcomes were evaluated 6, 24 and 48 h after pMCAO. First, we examined whether a bolus of MMF was capable of changing expression of kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor (Nrf)2 in the infarcted brain. Next, we studied the effect of MMF on functional recovery. To explore mechanisms potentially influencing functional changes, we examined infarct volumes, edema formation, the expression of heat shock protein (Hsp)72, hydroxycarboxylic acid receptor 2 (Hcar2), and inducible nitric oxide synthase (iNOS) in the infarcted brain using real-time PCR and Western blotting. Concentrations of a panel of pro- and anti-inflammatory cytokines (IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, TNF) were examined in both the infarcted brain tissue and plasma samples 6, 24 and 48 h after pMCAO using multiplex electrochemoluminiscence analysis. Results Administration of MMF increased the protein level of Nrf2 6 h after pMCAO, and improved functional outcome at 24 and 48 h after pMCAO. MMF treatment did not influence infarct size, however reduced edema volume at both 24 and 48 h after pMCAO. MMF treatment resulted in increased Hsp72 expression in the brain 6 h after pMCAO. Hcar2 mRNA levels increased significantly 24 h after pMCAO, but were not different between saline- and MMF-treated mice. MMF treatment also increased the level of the anti-inflammatory cytokine IL-10 in the brain and plasma 6 h after pMCAO, and additionally reduced the level of the pro-inflammatory cytokine IL-12p70 in the brain at 24 and 48 h after pMCAO. Conclusions A single intravenous bolus of MMF improved sensory-motor function after ischemic stroke, reduced edema formation, and increased the levels of the neuroprotective protein Hsp72 in the brain. The early increase in IL-10 and reduction in IL-12p70 in the brain combined with changes in systemic cytokine levels may also contribute to the functional recovery after pMCAO.
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| 3. |
- Scipioni, Roberto, et al.
(författare)
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Complementary analyses of aging in a commercial LiFePO4/graphite 26650 cell
- 2018
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Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 284, s. 454-468
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Tidskriftsartikel (refereegranskat)abstract
- In this work we investigate the electrode degradation mechanisms in a commercial 2.5 Ah LiFePO4/ graphite 26650 cylindrical cell. Aged and fresh electrode samples were prepared by cycling two cells respectively five and 22 k times. Subsequently the cells were disassembled in a glovebox and the electrode samples were prepared for electrochemical testing in a 3-electrode setup, and for characterization with XRD, XPS and low-kV FIB/SEM tomography. A 1 mu m thick CEI (cathode electrolyte interface) layer was observed at the electrode/electrolyte interface of the aged LiFePO4 electrode. Relative to the fresh LiFePO4 electrode, the aged electrode exhibited a larger series resistance which indicates the observed degradation layer increases the ionic resistance. In addition, micron-sized agglomerates, probably a mixture of carbonaceous material and decomposition products from the electrolyte, were observed at the electrode/electrolyte interface of the aged graphite electrode. These layers may contribute significantly to the loss of lithium inventory (LLI) in the cell, and to the loss of active material (LAM) in the graphite electrode. Low-voltage FIB/SEM tomography was used to detect local charging effects of graphite particles in the carbon electrode, an effect of poor dissipation of the electric charge to the ground after the sample interaction with the electron beam. The charging effects were primarily observed in the aged electrode and most of the locally charged particles were found to be close to the electrode/electrolyte interface, indicating a poorly percolating graphite network near this interface.
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