Mitochondrial dysfunction after experimental traumatic brain injury: Combined efficacy of SNX-111 and U-101033E

Y. Xiong, P. L. Peterson, B. H. Verweij, F. C. Vinas, Jan Paul Muizelaar, C. P. Lee

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


We recently demonstrated that posttraumatic administration of the N- type calcium channel blocker SNX-111 (S) and a novel blood-brain barrier penetrating antioxidant U-101033E (U), significantly alleviated mitochondrial dysfunction induced by traumatic brain injury (TBI) in rats. The present study was designed to determine whether a combination of S and U, which act on different biochemical mechanisms of secondary brain injury, would be more efficacious than either drug alone. Brain mitochondria from injured and uninjured hemispheres were isolated and examined at 12 h post TBI induced by a severe controlled cortical impact injury. S at 1.0 mg/kg significantly increased both State 3 and 4 rates and produced a slight increase in P/O ratio, and there was virtually no change in RCI. U at 1.0 mg/kg did not show any protection. However, the combined treatment of S at 1.0 mg/kg and U at 1.0 mg/kg eliminated the uncoupling effect of S, and restored not only State 3 rates and P/O ratios but also RCI to near sham values. These results provide further evidence that both reactive oxygen species and perturbation of cellular calcium homeostasis participate in the pathogenesis of TBI- induced mitochondrial dysfunction, and support the idea of using combined therapy with lower drug doses.

Original languageEnglish (US)
Pages (from-to)531-544
Number of pages14
JournalJournal of Neurotrauma
Issue number7
StatePublished - Jul 1998
Externally publishedYes


  • Antioxidants, brain mitochondria
  • Calcium channel blockers
  • Oxidative phosphorylation
  • Rats
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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