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Dichloroacetate tre...
Dichloroacetate treatment improves mitochondrial metabolism and reduces brain injury in neonatal mice
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- Sun, Yanyan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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- Li, Tao (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för hälsa och rehabilitering,Institute of Neuroscience and Physiology, Department of Health and Rehabilitation
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- Xie, Cuicui (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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- Zhang, Yaodong (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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- Zhou, Kai (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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- Wang, Xiaoyang, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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- Blomgren, Klas, 1963 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Zhu, Changlian, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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(creator_code:org_t)
- 2016-05-03
- 2016
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:22, s. 31708-31722
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https://gup.ub.gu.se...
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Abstract
Subject headings
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- The purpose of this study was to evaluate the effect of dichloroacetate (DCA) treatment for brain injury in neonatal mice after hypoxia ischemia (HI) and the possible molecular mechanisms behind this effect. Postnatal day 9 male mouse pups were subjected to unilateral HI, DCA was injected intraperitoneally immediately after HI, and an additional two doses were administered at 24 h intervals. The pups were sacrificed 72 h after HI. Brain injury, as indicated by infarction volume, was reduced by 54.2% from 10.8 +/- 1.9 mm(3) in the vehicle-only control group to 5.0 +/- 1.0 mm(3) in the DCA-treated group at 72 h after HI (p = 0.008). DCA treatment also significantly reduced subcortical white matter injury as indicated by myelin basic protein staining (p = 0.018). Apoptotic cell death in the cortex, as indicated by counting the cells that were positive for apoptosis-inducing factor (p = 0.018) and active caspase-3 (p = 0.021), was significantly reduced after DCA treatment. The pyruvate dehydrogenase activity and the amount of acetyl-CoA in mitochondria was significantly higher after DCA treatment and HI (p = 0.039, p = 0.024). In conclusion, DCA treatment reduced neonatal mouse brain injury after HI, and this appears to be related to the elevated activation of pyruvate dehydrogenase and subsequent increase in mitochondrial metabolism as well as reduced apoptotic cell death.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- apoptosis
- autophagy
- brain ischemia
- mitochondria
- pyruvate dehydrogenase
- Pathology Section
- hypoxic-ischemic encephalopathy
- congenital lactic-acidosis
- caloric
- restriction mimetics
- controlled clinical-trial
- in-vivo
- energy
- metabolites
- cerebral-ischemia
- cell-death
- autophagy
- neuroprotection
- ang lh
- 1992
- journal of cerebral blood flow and metabolism
- v12
- p1030
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sun, Yanyan
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Li, Tao
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Xie, Cuicui
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Zhang, Yaodong
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Zhou, Kai
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Wang, Xiaoyang, ...
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Blomgren, Klas, ...
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Zhu, Changlian, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Oncotarget
- By the university
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University of Gothenburg
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Karolinska Institutet