Kilbaugh 2016 Mitochondrion

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Kilbaugh TJ, Karlsson M, Duhaime AC, Hansson MJ, Elmer E, Margulies SS (2016) Mitochondrial response in a toddler-aged swine model following diffuse non-impact traumatic brain injury. Mitochondrion 26:19-25.

Β» PMID: 26549476 Open Access

Kilbaugh TJ, Karlsson M, Duhaime AC, Hansson MJ, Elmer E, Margulies SS (2016) Mitochondrion

Abstract: Traumatic brain injury (TBI) is an important health problem, and a leading cause of death in children worldwide. Mitochondrial dysfunction is a critical component of the secondary TBI cascades. Mitochondrial response in the pediatric brain has limited investigation, despite evidence that the developing brain's response differs from that of the adult, especially in diffuse non-impact TBI. We performed a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a swine model of diffuse TBI (rapid non-impact rotational injury: RNR), and examined the cortex and hippocampus. A substrate-uncoupler-inhibitor-titration protocol examined the role of the individual complexes as well as the uncoupled maximal respiration. Respiration per mg of tissue was also related to citrate synthase activity (CS) as an attempt to control for variability in mitochondrial content following injury. Diffuse RNR stimulated increased complex II-driven respiration relative to mitochondrial content in the hippocampus compared to shams. LEAK (State 4o) respiration increased in both regions, with decreased respiratory ratios of convergent oxidative phosphorylation through complex I and II, compared to sham animals, indicating uncoupling of oxidative phosphorylation at 24h. The study suggests that proportionately, complex I contribution to convergent mitochondrial respiration was reduced in the hippocampus after RNR, with a simultaneous increase in complex-II driven respiration. Mitochondrial respiration 24h after diffuse TBI varies by location within the brain. We concluded that significant uncoupling of oxidative phosphorylation and alterations in convergent respiration through complex I- and complex II-driven respiration reveals therapeutic opportunities for the injured at-risk pediatric brain.

Copyright Β© 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved. β€’ Keywords: In vivo studies, Large animal model of injury, Mitochondria, Pediatric brain injury, Traumatic brain injury

β€’ O2k-Network Lab: SE Lund Elmer E, US PA Philadelphia Margulies S

Labels: MiParea: Respiration, mt-Medicine  Pathology: Other 

Organism: Pig  Tissue;cell: Nervous system  Preparation: Homogenate 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 


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