Cyclosporin A, but not FK506, prevents the downregulation of phosphorylated Akt after transient focal ischemia in the rat

Brain Research
T YoshimotoB K Siesjö

Abstract

The two immunosuppressants, cyclosporin A (CsA) and FK506, when given 1 and 3 h after the start of reperfusion following 2 h of middle cerebral artery (MCA) occlusion, reduce infarct volume to 30% of control. This suggests a common effect, e.g. one due to suppression of the activation of calcineurin. However, when given by the intracarotid (i.c.) route after only 5 min of recirculation CsA, but not FK506, reduced infarct volume even further, to 10% of control. This was attributed to the fact that CsA, but not FK506, block the in vitro assembly of a mitochondrial permeability transition (MPT) pore. The present experiments were undertaken to further characterize the anti-ischemic effect of CsA, when given i.c. 5 min after recirculation and to explore why CsA, when given at that time, is more efficacious than FK506. It was established that the i.c. administration of CsA in a dose of 10 mg/kg increased the tissue concentration of CsA 2- to 3-fold, when compared to the i.v. administration. CsA proved to be effective in reducing infarct volume even when the tissue damage was assessed by histopathology after 7 days of recovery. MCA occlusion of 2 h duration caused a sustained decrease in the phosphorylation Akt at threonine 308. Since...Continue Reading

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Citations

Nov 17, 2010·Biochemistry. Biokhimii︠a︡·E E Dubinina, V A Dadali
Oct 4, 2005·The Journal of Clinical Investigation·Lisa Bouchier-HayesDonald D Newmeyer
Sep 1, 2008·Interdisciplinary Toxicology·Russel J ReiterDun-Xian Tan
Feb 9, 2008·Journal of the Neurological Sciences·Jun LiLouise D McCullough
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Apr 23, 2005·The European Journal of Neuroscience·Katarina G BryweHenrik Hagberg
Jan 20, 2006·The European Journal of Neuroscience·Changlian ZhuKlas Blomgren
Apr 20, 2004·Journal of Cellular and Molecular Medicine·Bozena KaminskaMalgorzata Zawadzka
Aug 16, 2005·Journal of Pineal Research·Ertugrul KilicDirk M Hermann
May 4, 2011·Brain Injury : [BI]·Minoru KawakamiBo K Siesjo
Dec 6, 2008·The Journal of Veterinary Medical Science·Phil-Ok Koh
Jan 18, 2006·Journal of Pharmacological Sciences·Tatsuo YamaguchiHiroyuki Uchino
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Sep 20, 2016·Critical Reviews in Toxicology·Xu WangZonghui Yuan

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