Effect of ischemic postconditioning against experimental global cerebral ischemia

Background. Ischemic postconditioning (IPost) has been recognized as an effective mechanism of protection against ischemia-reperfusion cerebral injury. However, a neuroprotective effect of IPost against prolonged global cerebral ischemia-reperfusion injury has not been studied yet. Objective. In the present study we investigated putative protective effect of IPost after prolonged global cerebral ischemia in Mongolian gerbils. Design and methods. Cerebral ischemia was induced using bilateral carotid artery occlusion method. Ischemic postconditioning was elicited by different numbers of ischemic and reperfusion stimuli of different duration after 30-min. global cerebral ischemia. Neurologic deficit and mortality were analyzed. Results. We demonstrated that neuroprotective effect of IPost is not evident after prolonged global ischemia in Mongolian gerbils. Moreover, the use of 2-min. ischemia/reperfusion stimuli for IPost after prolonged ischemia results in increased manifestations of neurologic deficit and increased mortality. Conclusion. IPost is not effective after prolonged global cerebral ischemia in Mongolian gerbils.

ischemic postconditioning, global cerebral ischemia, ischemia-reperfusion, brain, Mongolian gerbils

1. Sandercock P., Berge E., Dennis M. et al. A systematic review of the effectiveness, cost-effectiveness and barriers to implementation of thrombolytic and neuroprotective therapy for acute ischaemic stroke in the NHS // Health Technol. Assess. - 2002. - Vol. 6, № 26. - P. 1-112.

2.

3. Murry C.E., Jennings R.B., Reimer K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium // Circulation. - 1986. - Vol. 74, № 5. - P. 1124-1136.

4.

5. Zhao Z.Q., Corvera J.S., Halkos M.E. et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning // Am. J. Physiol. Heart Circ. Physiol. - 2003. - Vol. 285, № 2. - P. H579-H588.

6.

7. Vinten-Johansen J., Zhao Z.Q., Zatta A.J. et al. Postconditioning - a new link in nature's armor against myocardial ischemia-reperfusion injury // Basic Res. Cardiol. - 2005. - Vol. 100, № 4. - P. 295-310.

8.

9. Zhao H., Sapolsky R.M., Steinberg G.K. Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats // J. Cereb. Blood Flow Metab. - 2006. - Vol. 26, № 9. - P. 1114-1121.

10.

11. Rezkalla S.H., Kloner R.A. Preconditioning in humans // Heart Fail. Rev. - 2007. - Vol. 12, № 3-4. - P. 201-206.

12.

13. Mitani A., Kataoka K. Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study // Neuroscience. - 1991. - Vol. 42, № 3. - P. 661-670.

14.

15. McGraw C.P. Experimental cerebral infarction effects of pentobarbital in Mongolian gerbils // Arch. Neurol. - 1977. - Vol. 34, № 6. - P. 334-336.

16.

17. Ohno K., Ito U., Inaba Y. Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil // Brain Res. - 1984. - Vol. 297, № 1. - P.151-157.

18.

19. Levine S., Payan H. Effects of ischemia and other procedures on the brain and retina of the gerbil (Meriones unguiculatus) // Exp. Neurol. - 1966. - Vol. 16, № 3. - P. 255-262.

20.

21. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia // Brain Res. - 1982. - Vol. 239, № 1. - P. 57-69.

22.

23. Boengler K., Buechert A., Heinen Y. et al. Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice // Circ. Res. - 2008. - Vol. 102, № 1. - P. 131-135.

24.

25. Gao X., Ren C., Zhao H. Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning // J. Neurosci. Res. - 2008. - Vol. 86, № 11. - P. 2505-2511.

26.

27. Wang J., Shen J., Gao Q. et al. Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats // Stroke. - 2008. - Vol. 39, № 3. - P. 983-990.

28.

29. Jiang X., Shi E., Nakajima Y., Sato S. Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia // Ann Surg. - 2006. - Vol. 244, № 1. - P. 148 -153.