Sökning: onr:"swepub:oai:gup.ub.gu.se/325135" > Targeting succinate...
Fältnamn | Indikatorer | Metadata |
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000 | 03405naa a2200505 4500 | |
001 | oai:gup.ub.gu.se/325135 | |
003 | SwePub | |
008 | 240528s2023 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/3251352 URI |
024 | 7 | a https://doi.org/10.1016/j.redox.2023.1026002 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Mottahedin, Aminu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xmotam |
245 | 1 0 | a Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke |
264 | 1 | b Elsevier BV,c 2023 |
520 | a Current treatments for acute ischemic stroke aim to reinstate a normal perfusion in the ischemic territory but can also cause significant ischemia-reperfusion (IR) injury. Previous data in experimental models of stroke show that ischemia leads to the accumulation of succinate, and, upon reperfusion, the accumulated succinate is rapidly oxidized by succinate dehydrogenase (SDH) to drive superoxide production at mitochondrial complex I. Despite this process initiating IR injury and causing further tissue damage, the potential of targeting succinate metabolism to minimize IR injury remains unexplored. Using both quantitative and untargeted high -resolution metabolomics, we show a time-dependent accumulation of succinate in both human and mouse brain exposed to ischemia ex vivo. In a mouse model of ischemic stroke/mechanical thrombectomy mass spectrometry imaging (MSI) shows that succinate accumulation is confined to the ischemic region, and that the accumulated succinate is rapidly oxidized upon reperfusion. Targeting succinate oxidation by systemic infusion of the SDH inhibitor malonate upon reperfusion leads to a dose-dependent decrease in acute brain injury. Together these findings support targeting succinate metabolism upon reperfusion to decrease IR injury as a valuable adjunct to mechanical thrombectomy in ischemic stroke. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
653 | a reperfusion injury | |
653 | a accumulation | |
653 | a adenosine | |
653 | a Biochemistry & Molecular Biology | |
700 | 1 | a Prag, H. A.4 aut |
700 | 1 | a Dannhorn, A.4 aut |
700 | 1 | a Mair, R.4 aut |
700 | 1 | a Schmidt, C.4 aut |
700 | 1 | a Yang, M.4 aut |
700 | 1 | a Sorby-Adams, A.4 aut |
700 | 1 | a Lee, J. J.4 aut |
700 | 1 | a Burger, N.4 aut |
700 | 1 | a Kulaveerasingam, D.4 aut |
700 | 1 | a Huang, M. M.4 aut |
700 | 1 | a Pluchino, S.4 aut |
700 | 1 | a Peruzzotti-Jametti, L.4 aut |
700 | 1 | a Goodwin, R.4 aut |
700 | 1 | a Frezza, C.4 aut |
700 | 1 | a Murphy, M. P.4 aut |
700 | 1 | a Krieg, T.4 aut |
710 | 2 | a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi4 org |
773 | 0 | t Redox Biologyd : Elsevier BVg 59q 59x 2213-2317 |
856 | 4 8 | u https://gup.ub.gu.se/publication/325135 |
856 | 4 8 | u https://doi.org/10.1016/j.redox.2023.102600 |
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