Induced mitochondrial failure in the feline brain: Implications for understanding acute post-traumatic metabolic events

Tobias Clausen, Alois Zauner, Joseph E. Levasseur, Ann C. Rice, Ross Bullock

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Objective: Recently, evidence has become available implicating mitochondrial failure as a crucial factor in the pathogenesis of acute brain damage following severe traumatic brain injury (TBI). However, it remains unclear how mitochondrial dysfunction affects cerebral metabolism. Therefore the aim of the study was to evaluate the impact of 'isolated' mitochondrial failure on local cerebral metabolism. Methods: Cerebral mitochondrial metabolism was blocked by local microdialysis perfusion with cyanide in seven cats. Local brain tissue oxygen tension (ptiO2), carbon dioxide tension (ptiCO2) and pH, as well as extracellular cerebral fluid, glucose, lactate, pyruvate and glutamate were monitored, using a Neurotrend sensor and microdialysis, respectively. Tissue oxygen consumption was measured in a microrespirometric system, and ultrastructural changes evaluated via electron microscopy. Results: Brain tissue oxygen tension increased from a baseline of 31 ± 9 mmHg to 84 ± 30 mmHg after 60 min of cyanide perfusion (P < 0.05), concomitant a decrease in oxygen consumption from 14.45 ± 3.91 μl/h/mg to 10.83 ± 1.74 μl/h/mg (P < 0.05). Brain tissue pH was decreased after 60 min of cyanide perfusion (6.83 ± 0.16) compared to baseline (7.07 ± 0.39) (P < 0.05), whereas ptiCO2 did not show significant changes. Lactate massively increased from a baseline of 599 ± 270 μmol/l to 2609 ± 1188 μmol/l immediately after cyanide perfusion (P < 0.05). The lactate:glucose ratio increased from 0.79 ± 0.15 before cyanide perfusion to 6.40 ± 1.44 at 40 min after cyanide perfusion (P < 0.05), while no significant changes in the lactate:pyruvate ratio could be observed. Glutamate increased from a baseline of 11.6 ± 7.2 μmol/l to 61.4 ± 44.7 μmol/l after cyanide perfusion (P < 0.05). Conclusion: The results of this study show that 'isolated' cerebral mitochondrial failure initiates changes in cerebral substrates and biochemistry, which are very similar to most of the changes seen after severe human head injury, except for the early fall in ptiO2, further indicating a crucial involvement of mitochondrial impairment in the development of brain damage after TBI.

Original languageEnglish (US)
Pages (from-to)35-48
Number of pages14
JournalBrain research
Issue number1
StatePublished - Jul 10 2001


  • Cerebral metabolism
  • Cyanide
  • Microdialysis
  • Mitochondrial failure
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)


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