PMID- 31244764
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 10
DP  - 2019
TI  - Comprehensive Profile of Acute Mitochondrial Dysfunction in a Preclinical Model 
      of Severe Penetrating TBI.
PG  - 605
LID - 10.3389/fneur.2019.00605 [doi]
LID - 605
AB  - Mitochondria constitute a central role in brain energy metabolism, and play a 
      pivotal role in the development of secondary pathophysiology and subsequent 
      neuronal cell death following traumatic brain injury (TBI). Under normal 
      circumstances, the brain consumes glucose as the preferred energy source for 
      adenosine triphosphate (ATP) production over ketones. To understand the 
      comprehensive picture of substrate-specific mitochondrial bioenergetics responses 
      following TBI, adult male rats were subjected to either 10% unilateral 
      penetrating ballistic-like brain injury (PBBI) or sham craniectomy (n = 5 animals 
      per group). At 24 h post-injury, mitochondria were isolated from pooled brain 
      regions (frontal cortex and striatum) of the ipsilateral hemisphere. 
      Mitochondrial bioenergetics parameters were measured ex vivo in the presence of 
      four sets of metabolic substrates: pyruvate+malate (PM), glutamate+malate (GM), 
      succinate (Succ), and beta-hydroxybutyrate+malate (BHBM). Additionally, 
      mitochondrial matrix dehydrogenase activities [i.e., pyruvate dehydrogenase 
      complex (PDHC), alpha-ketoglutarate dehydrogenase complex (alpha-KGDHC), and 
      glutamate dehydrogenase (GDH)] and mitochondrial membrane-bound dehydrogenase 
      activities [i.e., electron transport chain (ETC) Complex I, II, and IV] were 
      compared between PBBI and sham groups. Furthermore, mitochondrial coenzyme 
      contents, including NAD((t)) and FAD((t)), were quantitatively measured in both 
      groups. Collectively, PBBI led to an overall significant decline in the ATP 
      synthesis rates (43-50%; (*) p < 0.05 vs. sham) when measured using each of the 
      four sets of substrates. The PDHC and GDH activities were significantly reduced 
      in the PBBI group (42-53%; (*) p < 0.05 vs. sham), whereas no significant 
      differences were noted in alpha-KGDHC activity between groups. Both Complex I and 
      Complex IV activities were significantly reduced following PBBI (47-81%; (*) p < 
      0.05 vs. sham), whereas, Complex II activity was comparable between groups. The 
      NAD((t)) and FAD((t)) contents were significantly decreased in the PBBI group 
      (27-35%; (*) p < 0.05 vs. sham). The decreased ATP synthesis rates may be due to 
      the significant reductions in brain mitochondrial dehydrogenase activities and 
      coenzyme contents observed acutely following PBBI. These results provide a basis 
      for the use of "alternative biofuels" for achieving higher ATP production 
      following severe penetrating brain trauma.
FAU - Pandya, Jignesh D
AU  - Pandya JD
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
FAU - Leung, Lai Yee
AU  - Leung LY
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
AD  - Department of Surgery, Uniformed Services University of the Health Sciences, 
      Bethesda, MD, United States.
FAU - Yang, Xiaofang
AU  - Yang X
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
FAU - Flerlage, William J
AU  - Flerlage WJ
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
FAU - Gilsdorf, Janice S
AU  - Gilsdorf JS
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
FAU - Deng-Bryant, Ying
AU  - Deng-Bryant Y
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
FAU - Shear, Deborah A
AU  - Shear DA
AD  - Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United 
      States.
LA  - eng
PT  - Journal Article
DEP - 20190611
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC6579873
OTO - NOTNLM
OT  - alternative biofuels
OT  - brain energy metabolism
OT  - dehydrogenase activities
OT  - energy crisis
OT  - mitochondria preferred substrates
OT  - penetrating ballistic-like brain injury (PBBI)
OT  - therapeutics
OT  - traumatic brain injury (TBI)
EDAT- 2019/06/28 06:00
MHDA- 2019/06/28 06:01
PMCR- 2019/06/11
CRDT- 2019/06/28 06:00
PHST- 2018/07/26 00:00 [received]
PHST- 2019/05/22 00:00 [accepted]
PHST- 2019/06/28 06:00 [entrez]
PHST- 2019/06/28 06:00 [pubmed]
PHST- 2019/06/28 06:01 [medline]
PHST- 2019/06/11 00:00 [pmc-release]
AID - 10.3389/fneur.2019.00605 [doi]
PST - epublish
SO  - Front Neurol. 2019 Jun 11;10:605. doi: 10.3389/fneur.2019.00605. eCollection 
      2019.