Impaired cortical mitochondrial function following TBI precedes behavioral changes

Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last...

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Main Authors:	Watson, William D., Buonora, John E., Yarnell, Angela M., Lucky, Jessica J., D’Acchille, Michaela I., McMullen, David C., Boston, Andrew G., Kuczmarski, Andrew V., Kean, William S., Verma, Ajay, Grunberg, Neil E., Cole, Jeffrey T.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912469/

id	pubmed-3912469
recordtype	oai_dc
spelling	pubmed-39124692014-02-18 Impaired cortical mitochondrial function following TBI precedes behavioral changes Watson, William D. Buonora, John E. Yarnell, Angela M. Lucky, Jessica J. D’Acchille, Michaela I. McMullen, David C. Boston, Andrew G. Kuczmarski, Andrew V. Kean, William S. Verma, Ajay Grunberg, Neil E. Cole, Jeffrey T. Neuroscience Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. Frontiers Media S.A. 2014-02-04 /pmc/articles/PMC3912469/ /pubmed/24550822 http://dx.doi.org/10.3389/fnene.2013.00012 Text en Copyright © 2014 Watson, Buonora, Yarnell, Lucky, D’Acchille, McMullen, Boston, Kuczmarski, Kean, Verma, Grunberg and Cole. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Watson, William D. Buonora, John E. Yarnell, Angela M. Lucky, Jessica J. D’Acchille, Michaela I. McMullen, David C. Boston, Andrew G. Kuczmarski, Andrew V. Kean, William S. Verma, Ajay Grunberg, Neil E. Cole, Jeffrey T.
spellingShingle	Watson, William D. Buonora, John E. Yarnell, Angela M. Lucky, Jessica J. D’Acchille, Michaela I. McMullen, David C. Boston, Andrew G. Kuczmarski, Andrew V. Kean, William S. Verma, Ajay Grunberg, Neil E. Cole, Jeffrey T. Impaired cortical mitochondrial function following TBI precedes behavioral changes
author_facet	Watson, William D. Buonora, John E. Yarnell, Angela M. Lucky, Jessica J. D’Acchille, Michaela I. McMullen, David C. Boston, Andrew G. Kuczmarski, Andrew V. Kean, William S. Verma, Ajay Grunberg, Neil E. Cole, Jeffrey T.
author_sort	Watson, William D.
title	Impaired cortical mitochondrial function following TBI precedes behavioral changes
title_short	Impaired cortical mitochondrial function following TBI precedes behavioral changes
title_full	Impaired cortical mitochondrial function following TBI precedes behavioral changes
title_fullStr	Impaired cortical mitochondrial function following TBI precedes behavioral changes
title_full_unstemmed	Impaired cortical mitochondrial function following TBI precedes behavioral changes
title_sort	impaired cortical mitochondrial function following tbi precedes behavioral changes
description	Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912469/
_version_	1612054280624144384

Impaired cortical mitochondrial function following TBI precedes behavioral changes

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