Display options
Share it on

EXCLI J. 2012 Apr 30;11:188-97. eCollection 2012.

The role of protein kinase C in ischemic tolerance induced by hyperoxia in rats with stroke.

EXCLI journal

Firoozeh Alavian, Sohrab Hajizadeh, Mohammad Reza Bigdeli, Mohammad Javan

Affiliations

  1. Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  2. Department of Biology, Shahid Beheshti University, Tehran, Iran.

PMID: 27385957 PMCID: PMC4932887

Abstract

Recent studies suggest that normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion (IR) injury. Protein kinase C (PKC) is a key signaling molecule involved in protection against IR injury but its role in protective effect of HO in brain injury in unknown. In this study we attempted to see if PKC is involved in the effect of HO. Rats were divided into four main experimental groups. The first two were exposed to 95 % oxygen (HO) in a chamber 4 h/day for 6 consecutive days. Each of these groups had a control group exposed to 21 % oxygen. To investigate the role of PKC during HO, chelerythrin chloride (CHEL, 1 mg/kg/day), a PKC inhibitor, or its vehicle was given to animals for 6 days. After 24 h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion neurological deficit scores, infarct volume, brain edema and blood-brain Barrier (BBB) permeability were assessed. HO decreased the infarct volume and brain edema in comparison with controls. PKC inhibition was associated with a significant increase in infarct size in both HO and control animals. PKC inhibition was unable to change brain edema in the experimental groups. Both HO and PKC inhibition reduced the BBB permeability within 24 h post occlusion of middle cerebral artery. Although both HO and PKC inhibition were associated with inhibition of BBB permeability during ischemic brain injury in rats, the neuroprotective effect of HO was independent of PKC in the MCAO model.

Keywords: PKC; chelerythrin chloride; ischemic preconditioning; neuroprotection; normobaric hyperoxia; stroke

References

  1. Brain Res. 2007 Jun 4;1152:228-33 - PubMed
  2. J Pharmacol Sci. 2004 Nov;96(3):264-70 - PubMed
  3. Brain Res Mol Brain Res. 2001 Nov 1;95(1-2):110-6 - PubMed
  4. Stroke. 2002 Jun;33(6):1706-11 - PubMed
  5. Neurosci Lett. 1992 May 11;139(1):118-21 - PubMed
  6. Stroke. 1989 Jan;20(1):84-91 - PubMed
  7. J Cereb Blood Flow Metab. 2002 Nov;22(11):1283-96 - PubMed
  8. Lancet. 1997 May 3;349(9061):1269-76 - PubMed
  9. J Cereb Blood Flow Metab. 2005 May;25(5):554-71 - PubMed
  10. Neurology. 1997 Feb;48(2):306-11 - PubMed
  11. J Pharmacol Exp Ther. 2003 May;305(2):482-94 - PubMed
  12. Am J Physiol. 1993 Jan;264(1 Pt 2):H33-9 - PubMed
  13. Stroke. 1997 Nov;28(11):2303-9; discussion 2310 - PubMed
  14. Eur J Pharmacol. 2009 Jun 2;611(1-3):22-9 - PubMed
  15. Circ Res. 1999 May 14;84(9):1095-109 - PubMed
  16. Brain Res. 1992 Dec 25;599(2):246-52 - PubMed
  17. J Thorac Cardiovasc Surg. 2003 Mar;125(3):650-60 - PubMed
  18. Neuroscience. 1996 Dec;75(3):687-94 - PubMed
  19. Stroke. 2003 Sep;34(9):2252-7 - PubMed
  20. Expert Rev Mol Med. 2009 Jun 30;11:e19 - PubMed
  21. Am J Physiol. 1990 Dec;259(6 Pt 2):H1822-5 - PubMed
  22. Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2012-9 - PubMed
  23. Brain Res. 1990 Sep 24;528(1):21-4 - PubMed
  24. Neuroscience. 2002;115(1):173-83 - PubMed
  25. Biochem Cell Biol. 1991 May-Jun;69(5-6):375-82 - PubMed
  26. Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1150-7 - PubMed
  27. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11981-6 - PubMed
  28. Life Sci. 2003 Nov 7;73(25):3235-44 - PubMed
  29. J Cereb Blood Flow Metab. 1990 Mar;10(2):290-3 - PubMed

Publication Types