Attenuation of mitochondrial dysfunction by a novel blood-brain barrier permeable antioxidant (U-101033E) following traumatic brain injury in rats

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

Research output: Contribution to journalArticle

Abstract

With the GM controlled cortical impact rat model we have shown that traumatic brain injury (TBI) perturbs cellular Ca2 homeostasis and results in impairment in brain mitochondrial electron transfer and energy transduction, which occur at 1 hr and persist for at least 14 days with maximal injury at 1272 hr (Xiong et al. J Neurotrauma 14 23, 1997). The efficacy of U101033F. (U) on TBI-induced mitochondrial dysfunction is presented. Two boluses II 1-10 mg/kg) were iv given at 5 min and 2 hr post TBI. Brain mitochondria were isolated 12 hr post TBI, and assayed (± EGTA) for electron transfer and energy transfer activities. U restored the activities partially (- EGTA), and fully (+ EGTA) to sham levels. U exhibited a bellshaped dose response curve with an optimal dose of 3 mg/kg (n-5, p< 0.05 v.v vehicle) When mitochondria were assayed (+ EGTA) at varying times (6 hr14 days) post TBI in rats receiving 3 mg U/kg, the electron transfer and energy coupling activities were fully restored in all cases tested. Our data indicate that U-101033E at proper dosage can effectively attenuate TBIinduced mitochondrial dysfunction, and support the contention that oxidative stress and perturbation of cellular Ca2 homeostasis contribute to TBI-induced pathogenesis Supported by Pharmacia/I pjohn Pharmaceutical Co.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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