Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats

Beat Alessandri, Ann C. Rice, Joseph Levasseur, Michelle DeFord, Robert J. Hamm, M. Ross Bullock

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Traumatic brain injury (TBI) triggers a complex pathophysiological cascade, leading to cell death. A major factor in the pathogenesis of TBI is neuronal overloading with calcium, causing the opening of mitochondrial permeability transition pores (MPTP), which consequently inhibit normal mitochondrial function. The immunosuppressant Cyclosporin A (CsA) has been shown to block MPTPs, and to be neuroprotective in ischemia and TBI. However, the translation of these effects on mitochondrial function, into behavioral endpoints has not been investigated thoroughly. Therefore, we tested the effect of a low, clinically evaluated, CsA dose of 0.125 mg/kg (infused for 3 h) and a higher "known" neuroprotective dose of 18.75 mg/kg on brain tissue O2 consumption, and on motor and cognitive performance following lateral fluid percussion injury (FPI) in rats. CsA at both concentrations abolished the 25% decrease in O2 consumption (VO2), seen in saline-treated animals at 5 h post-FPI. Furthermore, the lower dose of CsA also ameliorated acute motor deficits (days 1-5 post-FPI) and learning and memory impairments in a Morris water maze test on days 11-15 post-FPI. Although, the higher dose of CsA improved cognitive performance, it worsened acute motor functional recovery. These results suggest, that the CsA-induced preservation of mitochondrial function, as assessed by tissue O2 consumption, directly translated into improvements in motor and cognitive behavior.

Original languageEnglish (US)
Pages (from-to)829-841
Number of pages13
JournalJournal of neurotrauma
Volume19
Issue number7
DOIs
StatePublished - Jul 2002

Keywords

  • Behavior
  • Cyclosporin A
  • Fluid percussion injury
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats'. Together they form a unique fingerprint.

  • Cite this