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Disease Outcome and...
Disease Outcome and Brain Metabolomics of Cyclophilin-D Knockout Mice in Sepsis
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- Kobayashi, Takayuki (author)
- Tokyo Medical University
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- Uchino, Hiroyuki (author)
- Tokyo Medical University
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- Elmér, Eskil (author)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups
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- Ogihara, Yukihiko (author)
- Tokyo Medical University
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Fujita, Hidetoshi (author)
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- Sekine, Shusuke (author)
- Tokyo Medical University
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- Ishida, Yusuke (author)
- Tokyo Medical University
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- Saiki, Iwao (author)
- Tokyo Medical University
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- Shibata, Shoichiro (author)
- Tokyo Medical University
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- Kawachi, Aya (author)
- Tokyo Medical University
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(creator_code:org_t)
- 2022-01-16
- 2022
- English.
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:2
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Abstract
Subject headings
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- Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Cyclophilin D
- Encephalopathy
- Glutathione
- Mitochondria
- Oxidative stress
Publication and Content Type
- art (subject category)
- ref (subject category)
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Kobayashi, Takay ...
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Uchino, Hiroyuki
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Elmér, Eskil
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Ogihara, Yukihik ...
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Fujita, Hidetosh ...
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Sekine, Shusuke
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Ishida, Yusuke
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Saiki, Iwao
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Shibata, Shoichi ...
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Kawachi, Aya
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- MEDICAL AND HEALTH SCIENCES
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and Clinical Medicin ...
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and Surgery
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and Neurosciences
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Lund University