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Article Open Access

Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury

  • Authors:
    • Danyun Fu
    • Haitong Liu
    • Hua Liu
    • Junyan Yao
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Shanghai General Hospital, Shanghai 200080, P.R. China
    Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4811-4820
    |
    Published online on: October 7, 2019
       https://doi.org/10.3892/mmr.2019.10729
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Abstract

It has recently been revealed that during the aorta‑clamped period, D‑Ala2, D‑Leu5‑Enkephalin (DADLE) infusion can protect the spinal cord against ischemia and reperfusion (I/R) injury. However, the protective effects of DADLE administration prior to ischemia or at the time of early reperfusion have not yet been investigated. Drug pre‑ or post‑conditioning can serve as a more valuable clinical strategy. Therefore, the present study was designed to investigate the neuroprotective effect of DADLE infusion at different time intervals in order to determine the optimum time point for ischemic spinal cord protection. A total of 40 New Zealand white rabbits were randomly divided into 5 groups: Sham‑operated (Sham), normal saline pre‑conditioning (NS), DADLE per‑conditioning (Dper), DADLE pre‑conditioning (Dpre) and DADLE post‑conditioning (Dpost). All animals were subjected to spinal cord ischemia for 30 min followed by 48 h reperfusion. Hind limb motor functions were assessed according to the Tarlov criterion when the animals regained consciousness, 6, 24 and 48 h after reperfusion. Histological analysis and the number of viable α‑motor neurons were also used to assess the extent of spinal cord injury. Compared with the NS group, the Tarlov scores and the number of normal neurons were significantly higher in the Dper group (P<0.05), which were consistent with the results of a previous study. In addition, the paraplegia rate and loss of normal motor neurons were lower in the DADLE per‑ and post‑conditioning groups compared with the DADLE pre‑conditioning; however, these were not statistically significant. DADLE 0.05 mg/kg administration at three time points all mitigated normal motor neuron injury in the anterior horn and decreased the paraplegia rates in rabbits. The therapeutic benefits appeared best in the post‑conditioning group with DADLE, and worst in the pre‑conditioning group.
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1 

Zvara DA: Thoracoabdominal aneurysm surgery and the risk of paraplegia: Contemporary practice and future directions. J Extra Corpor Technol. 34:11–17. 2002.PubMed/NCBI

2 

Ballard JL: Thoracoabdominal aortic aneurysm repair: Historical review and description of a re-engineered technique. Perspect Vasc Surg Endovasc Ther. 17:207–215. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Mehmedagic I, Resch T and Acosta S: Complications to cerebrospinal fluid drainage and predictors of spinal cord ischemia in patients with aortic disease undergoing advanced endovascular therapy. Vasc Endovascular Surg. 47:415–422. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, et al: Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials. Lancet. 370:1483–1493. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW and Stone GW: Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: The AMISTAD-2 trial. Eur Heart J. 27:2400–2405. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Danielisova V, Gottlieb M, Nemethova M, Kravcuková P, Domoráková I, Mechírová E and Burda J: Bradykinin postconditioning protects pyramidal CA1 neurons against delayed neuronal death in rat hippocampus. Cell Mol Neurobiol. 29:871–878. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Li L and Zuo Z: Isoflurane postconditioning induces neuroprotection via Akt activation and attenuation of increased mitochondrial membrane permeability. Neuroscience. 199:44–50. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Yu QJ, Zhou QS, Huang HB, Wang YL, Tian SF and Duan DM: Protective effect of ketamine on ischemic spinal cord injury in rabbits. Ann Vasc Surg. 22:432–439. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Charron C, Messier C and Plamondon H: Neuroprotection and functional recovery conferred by administration of kappa- and delta 1-opioid agonists in a rat model of global ischemia. Physiol Behav. 93:502–511. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Schultz JE, Rose E, Yao Z and Gross GJ: Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol. 268:H2157–H2161. 1995.PubMed/NCBI

11 

Zatta AJ, Kin H, Yoshishige D, Jiang R, Wang N, Reeves JG, Mykytenko J, Guyton RA, Zhao ZQ, Caffrey JL and Vinten-Johansen J: Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Am J Physiol Heart Circ Physiol. 294:H1444–H1451. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Borlongan CV, Wang Y and Su TP: Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: Linking hibernation and neuroprotection. Front Biosci. 9:3392–3398. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Su DS, Wang ZH, Zheng YJ, Zhao YH and Wang XR: Dose-dependent neuroprotection of delta opioid peptide [D-Ala2, D-Leu5] enkephalin in neuronal death and retarded behavior induced by forebrain ischemia in rats. Neurosci Lett. 423:113–117. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Wang S, Duan Y, Su D, Li W, Tan J, Yang D, Wang W, Zhao Z and Wang X: Delta opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia. Eur J Pharmacol. 658:140–144. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Liu H, Chen B, Li S and Yao J: Dose-dependent neuroprotection of delta-opioid peptide [D-Ala(2), D-Leu(5)] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits. J Vasc Surg. 63:1074–1081. 2016. View Article : Google Scholar : PubMed/NCBI

16 

National Research Council (US) Institute for Laboratory Animal Research: Guide for the care and use of laboratory animalsWashington (DC): National Academies Press (US); 1996

17 

Liu H, Chen B, Zhang Y, Qiu Y, Xia Y, Li S and Yao J: Protective effect of delta opioid agonist [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia reperfusion injury by regional perfusion into abdominal aorta in rabbits. Neurosci Lett. 584:1–6. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Tarlov IM: Acute spinal cord compression paralysis. J Neurosurg. 36:10–20. 1972. View Article : Google Scholar : PubMed/NCBI

19 

Ehrlich M, Knolle E, Ciovica R, Böck P, Turkof E, Grabenwöger M, Cartes-Zumelzu F, Kocher A, Pockberger H, Fang WC, et al: Memantine for prevention of spinal cord injury in a rabbit model. J Thorac Cardiovasc Surg. 117:285–291. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Apaydin AZ and Buket S: Regional lidocaine infusion reduces postischemic spinal cord injury in rabbits. Tex Heart Inst J. 28:172–176. 2001.PubMed/NCBI

21 

Yao JY, Weng H, Zhang L, Wang QY, Yuan YQ, Tang Y and Li JS: The reperfusion injury model improvement and the tolerance time investigation of rabbit spinal cord ischemia under normothermia. Sichuan Da Xue Xue Bao Yi Xue Ban. 38:497–500, 542. 2007.(In Chinese). PubMed/NCBI

22 

Hamaishi M, Orihashi K, Isaka M, Kumagai H, Takahashi S, Okada K, Ohtaki M and Sueda T: Low-dose edaravone injection into the clamped aorta prevents ischemic spinal cord injury. Ann Vasc Surg. 23:128–135. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Fuardo M, Lemoine S, Lo Coco C, Hanouz JL and Massetti M: [D-Ala2,D-Leu5]-enkephalin (DADLE) and morphine-induced postconditioning by inhibition of mitochondrial permeability transition pore, in human myocardium. Exp Biol Med (Maywood). 238:426–432. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Hausenloy DJ and Yellon DM: Preconditioning and postconditioning: Underlying mechanisms and clinical application. Atherosclerosis. 204:334–341. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Toumpoulis IK, Papakostas JC, Matsagas MI, Malamou-Mitsi VD, Pappa LS, Drossos GE, Derose JJ and Anagnostopoulos CE: Superiority of early relative to late ischemic preconditioning in spinal cord protection after descending thoracic aortic occlusion. J Thorac Cardiovasc Surg. 128:724–730. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Zvara DA, Colonna DM, Deal DD, Vernon JC, Gowda M and Lundell JC: Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia. Ann Thorac Surg. 68:874–880. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA and Vinten-Johansen J: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 285:H579–H588. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Chen Z, Li T and Zhang B: Morphine postconditioning protects against reperfusion injury in the isolated rat hearts. J Surg Res. 145:287–294. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Ma MC, Qian H, Ghassemi F, Zhao P and Xia Y: Oxygen-sensitive {delta}-opioid receptor-regulated survival and death signals: Novel insights into neuronal preconditioning and protection. J Biol Chem. 280:16208–16218. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Lee HJ and Amidon GL: The effect of enzyme inhibitor and absorption site following [D-ala2, D-leu5]enkephalin oral administration in rats. Biopharm Drug Dispos. 23:131–141. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Krassioukov AV, Karlsson AK, Wecht JM, Wuermser LA, Mathias CJ and Marino RJ; Joint Committee of American Spinal Injury Association and International Spinal Cord Society, : Assessment of autonomic dysfunction following spinal cord injury: Rationale for additions to international standards for neurological assessment. J Rehabil Res Dev. 44:103–112. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Santillan A, Nacarino V, Greenberg E, Riina HA, Gobin YP and Patsalides A: Vascular anatomy of the spinal cord. J Neurointerv Surg. 4:67–74. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Seppälä M, Antinheimo J, Pohjola J and Hernesniemi J: Acute spinal cord compression. Duodecim. 129:2655–2660. 2013.(In Finnish). PubMed/NCBI

34 

Tian J, Gu Y, Sun K, Wang B, Chen J, Wang X and Su D: [D-Ala2, D-Leu5] encephalin (DADLE) reversibly inhibits cellular transcription in neurons without causing cell injury. Brain Res. 1565:1–7. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Fu D, Liu H, Li S, Chen L and Yao J: Antioxidative and antiapoptotic effects of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia-reperfusion injury in rabbits. Front Neurosci. 11:6032017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Fu D, Liu H, Liu H and Yao J: Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury. Mol Med Rep 20: 4811-4820, 2019.
APA
Fu, D., Liu, H., Liu, H., & Yao, J. (2019). Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury. Molecular Medicine Reports, 20, 4811-4820. https://doi.org/10.3892/mmr.2019.10729
MLA
Fu, D., Liu, H., Liu, H., Yao, J."Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury". Molecular Medicine Reports 20.6 (2019): 4811-4820.
Chicago
Fu, D., Liu, H., Liu, H., Yao, J."Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury". Molecular Medicine Reports 20, no. 6 (2019): 4811-4820. https://doi.org/10.3892/mmr.2019.10729
Copy and paste a formatted citation
x
Spandidos Publications style
Fu D, Liu H, Liu H and Yao J: Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury. Mol Med Rep 20: 4811-4820, 2019.
APA
Fu, D., Liu, H., Liu, H., & Yao, J. (2019). Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury. Molecular Medicine Reports, 20, 4811-4820. https://doi.org/10.3892/mmr.2019.10729
MLA
Fu, D., Liu, H., Liu, H., Yao, J."Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury". Molecular Medicine Reports 20.6 (2019): 4811-4820.
Chicago
Fu, D., Liu, H., Liu, H., Yao, J."Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury". Molecular Medicine Reports 20, no. 6 (2019): 4811-4820. https://doi.org/10.3892/mmr.2019.10729
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