Amelioration of mitochondrial function by a novel antioxidant U-101033E following traumatic brain injury in rats

Y. Xiong, P. L. Peterson, Jan Paul Muizelaar, C. P. Lee

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


In the present study, a severe traumatic brain injury (TBI) was produced over the right parietal cortex of rats using the controlled cortical impact injury (CCII) model. TBI perturbed calcium homeostasis and impaired electron transfer and energy coupling activities of forebrain mitochondria isolated from injured hemispheres with a maximal injury at 12-72 h. Efficacy of the bloodbrain barrier penetrating antioxidant U-101033E on TBI-induced mitochondrial impairment was evaluated. In the dose-response experiment, two i.v. boluses (vehicle or 1-10 mg/kg of U-101033E) were administered at 5 min and 2h post-TBI. Forebrain mitochondria from each hemisphere were examined at 12 h post-injury. With respect to forebrain mitochondrial dysfunction, the drug showed a bell-shaped dose-response curve with an optimal dose of 3 mg/kg (n = 5, p < 0.05 vs. vehicle). In the time-course experiment, two i.v. boluses of 3 mg U-101033E/kg (the optimal dose) were given at 5 min and 2 h post-injury and forebrain mitochondria were examined at 6 h-14 days post- injury. U-101033E significantly restored electron transfer, energy coupling capacity, and Ca2+ transport capacity during 6 h to 14 days post-injury. Our data indicate that the antioxidant U-101033E administered post-injury at proper dosage can effectively restore TBI-induced mitochondrial dysfunction and support the contention that oxidative stress plays an important role in the pathogenesis of TBI.

Original languageEnglish (US)
Pages (from-to)907-917
Number of pages11
JournalJournal of Neurotrauma
Issue number12
StatePublished - Dec 1997
Externally publishedYes


  • Antioxidants
  • Brain mitochondria
  • Calcium
  • Oxidative phosphorylation
  • Rats
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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