Effect of Anesthetics on Efficiency of Remote Ischemic Preconditioning

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D. N. Silachev^1#, E. A. Usatikova^1#, I. B. Pevzner¹, L. D. Zorova^1,2, V. A. Babenko³, M. V. Gulyaev⁴, Yu. A. Pirogov⁵, E. Yu. Plotnikov¹, and D. B. Zorov^1*

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; E-mail: zorov@genebee.msu.ru

²International Laser Center, Lomonosov Moscow State University, 119992 Moscow, Russia

³Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119992 Moscow, Russia

⁴Lomonosov Moscow State University, Faculty of Fundamental Medicine, 119992 Moscow, Russia

⁵Lomonosov Moscow State University, Faculty of Physics, 119992 Moscow, Russia

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received October 28, 2016; Revision received May 4, 2017

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Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3β, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3β. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection.

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KEY WORDS: ischemia, brain, remote preconditioning, hind limb, chloral hydrate, Zoletil

DOI: 10.1134/S0006297917090036

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