Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

@article{Kajimoto2014PropofolCW,
  title={Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex},
  author={Masaki Kajimoto and Douglas B Atkinson and Dolena Ledee and Ernst-Bernhard Kayser and Philip G. Morgan and Margaret M Sedensky and Nancy G. Isern and Christine Des Rosiers and Michael A. Portman},
  journal={Journal of Cerebral Blood Flow \& Metabolism},
  year={2014},
  volume={34},
  pages={514 - 521}
}
Anesthetics used in infants and children are implicated in the development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in immature swine anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon-labeled glucose and leucine in the common carotid artery to assess citric acid cycle (CAC) metabolism in… 
Anesthesia-Sepsis-Associated Alterations in Liver Gene Expression Profiles and Mitochondrial Oxidative Phosphorylation Complexes
TLDR
Rats anesthetized with isoflurane exhibit more oxidative stress, decreased oxidative phosphorylation protein expression, and electron transport chain activity and increased expression of organ-protective proteins following exposure to Sepsis-inflammation.
Impact of inflammation on brain subcellular energetics in anesthetized rats
TLDR
In the setting of inflammation, rats exposed to isoflurane show increased Hypoxia-inducible factor-1α expression despite a lack of hypoxia, increased oxidative stress in the brain, and increased serum lactate, all of which suggest a relative increase in anaerobic metabolism compared to propofol.
Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner
TLDR
It is demonstrated that clinically relevant concentrations of propofol, used within a clinically relevant exposure time, suppressed the mitochondrial function, caused the generation of reactive oxygen species, and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting complexes I and III of mitochondria.
Sevoflurane Effects on Neuronal Energy Metabolism Correlate with Activity States While Mitochondrial Function Remains Intact
TLDR
Integration of experimental data and computer modeling revealed no evidence for a direct effect of sevoflurane on key enzymes of the citric acid cycle or oxidative phosphorylation, and mitochondrial function remained intact under sev oflurain, suggesting a better metabolic profile than isofluane or propofol.
Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion
  • M. KajimotoD. Ledee M. Portman
  • Biology, Medicine
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2016
TLDR
The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis.
In vivo study of hepatic oxidative stress and mitochondrial function in rabbits with severe hypotension after propofol prolonged infusion
TLDR
The results suggest that lipid-based emulsions can be involved in the regulation of different pathways that ultimately lead to a decrease of state 3 mitochondrial respiration rate in rabbits, using the rabbit as animal model.
Propofol induces impairment of mitochondrial biogenesis through inhibiting the expression of peroxisome proliferator–activated receptor‐γ coactivator‐1α
TLDR
The results demonstrate that clinically relevant doses of propofol reduce the expression of peroxisome proliferator–activated receptor‐γ coactivator‐1 α (PGC‐1α) in a dose‐ and time‐dependent manner and that PGC‐1β is the central mediator of prop ofol‐induced impairment of mitochondrial biogenesis and neuronal mitochondrial dysfunction.
Recent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies
TLDR
The evidence of neurotoxicity from animal models, animal cell culture, and human stem cell–derived neuron culture studies, and the mechanism of propofol-induced developmental neurotoxicity, such as increased cell death in neurons and oligodendrocytes, dysregulation of neurogenesis, abnormal dendritic development, and decreases in neurotrophic factor expression are presented.
Propofol Prevents Oxidative Stress by Decreasing the Ischemic Accumulation of Succinate in Focal Cerebral Ischemia–Reperfusion Injury
TLDR
The protective effect of propofol appears to act, at least in part, by limiting oxidative stress injury by preventing the ischemic accumulation of succinate.
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