Skip to main content

Advertisement

SpringerLink
Log in

Effect of dexmedetomidine on cerebral ischemia-reperfusion rats by activating mitochondrial ATP-sensitive potassium channel

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

The aim of the study reported here was to evaluate whether the mitochondrial ATP-sensitive potassium (mitoKATP) channel could participate in the effect of dexmedetomidine on cerebral ischemia-reperfusion (I/R) rats. Forty rats were randomly assigned into 5 groups: sham operation (S) group; cerebral I/R group; dexmedetomidine (D) group; 5-hydroxydecanoate (5-HD) group; 5-HD + D group. The cerebral I/R were produced by 2 h right middle cerebral artery occlusion followed by 24 h reperfusion. Dexmedetomidine (50μg/kg) was injected intraperitoneally before ischemia and after the onset of reperfusion. 5-HD (30 mg/kg) was injected intraperitoneally at 1 h before ischemia. The neurological deficit score (NDS) and the levels of super oxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Compared to group S, NDS and the levels of MDA, MPO, IL-6 and TNF-α were significantly higher, and SOD levels were significantly lower in the other groups (P < 0.05). Compared to group I/R,NDS and the levels of MDA, MPO, IL-6 and TNF-α were significantly lower, and SOD level was significantly higher in group D (P < 0.05). Compared to group D, NDS and the levels of MDA, MPO, IL-6 and TNF-α were significantly higher, and SOD level was significantly lower in group5-HD + D (P < 0.05). The activation of the mitoKATP channel could contribute to the protective effect of dexmedetomidine on rats induced by focal cerebral ischemia-reperfusion injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Reference

  • Ahn MJ, Sherwood ER, Prough DS, Lin CY, DeWitt DS (2004) The effects of traumatic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression. J Neurotrauma 21:1431–1442

    Article  PubMed  Google Scholar 

  • Bajgar R, Seetharaman S, Kowaltowski AJ, Garlid KD, Paucek P (2001) Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain. J Biol Chem 276:33369–33374. doi:10.1074/jbc.M103320200

    Article  CAS  PubMed  Google Scholar 

  • Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28:1233–1244. doi:10.1161/01.STR.28.6.1233

  • Bates B et al (2002) Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress: possible involvement of oxygen free radicals. Neurobiol Dis 9:24–37. doi:10.1006/nbdi.2001.0458

    Article  CAS  PubMed  Google Scholar 

  • Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  CAS  PubMed  Google Scholar 

  • Clark WM, Rinker LG, Lessov NS, Hazel K, Eckenstein F (1999) Time course of IL-6 expression in experimental CNS ischemia. Neurol Res 21:287–292

    Article  CAS  PubMed  Google Scholar 

  • Debska G, May R, Kicinska A, Szewczyk A, Elger CE, Kunz WS (2001) Potassium channel openers depolarize hippocampal mitochondria. Brain Res 892:42–50

    Article  CAS  PubMed  Google Scholar 

  • del Zoppo GJ (2009) Inflammation and the neurovascular unit in the setting of focal cerebral ischemia. Neuroscience 158:972–982. doi:10.1016/j.neuroscience.2008.08.028

    Article  PubMed  Google Scholar 

  • Graham SH, Chen J (2001) Programmed cell death in cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 21:99–109. doi:10.1097/00004647-200102000-00001

    Article  CAS  Google Scholar 

  • Hagar H, Al Malki W (2014) Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: role of oxidative stress and caspase-3. Environ Toxicol Pharmacol 37:803–811. doi:10.1016/j.etap.2014.02.013

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP (1994) Regulation of mitochondrial metabolism through changes in matrix volume. Biochem Soc Trans 22:522–529

    Article  CAS  PubMed  Google Scholar 

  • Hanley PJ, Daut J (2005) K(ATP) channels and preconditioning: a re-examination of the role of mitochondrial K(ATP) channels and an overview of alternative mechanisms. J Mol Cell Cardiol 39:17–50. doi:10.1016/j.yjmcc.2005.04.002

    Article  CAS  PubMed  Google Scholar 

  • Hanley PJ et al (2005) 5-hydroxydecanoate is metabolised in mitochondria and creates a rate-limiting bottleneck for beta-oxidation of fatty acids. J Physiol 562:307–318. doi:10.1113/jphysiol.2004.073932

    Article  CAS  PubMed  Google Scholar 

  • Hoffman WE, Kochs E, Werner C, Thomas C, Albrecht RF (1991) Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole. Anesthesiology 75:328–332

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232–245. doi:10.1016/j.surneu.2005.12.028

    Article  PubMed  Google Scholar 

  • Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317. doi:10.1016/B978-0-12-394309-5.00006-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitamoto M et al (2011) Sairei-to ameliorates rat peritoneal fibrosis partly through suppression of oxidative stress nephron. Exp Nephrol 117:e71–e81. doi:10.1159/000321147

    Article  CAS  Google Scholar 

  • Kleemann R et al (2003) Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: evidence for antiinflammatory effects of rosuvastatin. Circulation 108:1368–1374. doi:10.1161/01.cir.0000086460.55494.af

    Article  CAS  PubMed  Google Scholar 

  • Kontos HA (2001) Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke; A J Cereb Circ 32:2712–2716

    Article  CAS  Google Scholar 

  • Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke; J Cereb Circ 25:1481–1488

    Article  CAS  Google Scholar 

  • Lu DQ, Chen Y, Li T, Li BL (2010) Role of protein kinase C in protecting rats against pulmonary ischemia reperfusion injury through opening of mitochondrial ATP sensitive potassium channel. Sichuan Da Xue Xue Bao Yi Xue Ban 41:436–440

    CAS  PubMed  Google Scholar 

  • Mao GX et al (2010) Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status. Mech Ageing Dev 131:723–731. doi:10.1016/j.mad.2010.10.003

    Article  CAS  PubMed  Google Scholar 

  • Mao GX et al (2012) Antiaging effect of pine pollen in human diploid fibroblasts and in a mouse model induced by D-galactose. Oxidative Med Cell Longev 2012:750963. doi:10.1155/2012/750963

    Article  Google Scholar 

  • Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, Kogure K (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of Neutrophil Depletion Stroke; J Cereb Circ 25:1469–1475

    Article  CAS  Google Scholar 

  • Pac-Soo CK, Mathew H, Ma D (2015) Ischaemic conditioning strategies reduce ischaemia/reperfusion-induced organ injury. Br J Anaesth 114:204–216. doi:10.1093/bja/aeu302

    Article  CAS  PubMed  Google Scholar 

  • Rajapakse N, Shimizu K, Kis B, Snipes J, Lacza Z, Busija D (2002) Activation of mitochondrial ATP-sensitive potassium channels prevents neuronal cell death after ischemia in neonatal rats. Neurosci Lett 327:208–212

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez MJ, Martinez-Moreno M, Ortega FJ, Mahy N (2013) Targeting microglial K(ATP) channels to treat neurodegenerative diseases: a mitochondrial issue. Oxidative Med Cell Longev 2013:194546. doi:10.1155/2013/194546

    Article  Google Scholar 

  • Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Huttemann M (2013) Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol 47:9–23. doi:10.1007/s12035-012-8344-z

    Article  CAS  Google Scholar 

  • Sheng H, Bart RD, Oury TD, Pearlstein RD, Crapo JD, Warner DS (1999) Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia. Neuroscience 88:185–191

    Article  CAS  PubMed  Google Scholar 

  • Sun H-s, Feng Z-p (2013) Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia. Acta Pharmacol Sin 34:24–32

    Article  PubMed  Google Scholar 

  • Sun GY, Hu ZY (1995) Stimulation of phospholipase A2 expression in rat cultured astrocytes by LPS, TNF alpha and IL-1 beta. Prog Brain Res 105:231–238

    Article  CAS  PubMed  Google Scholar 

  • Szewczyk A, Marbán E (1999) Mitochondria: a new target for K+ channel openers? Trends Pharmacol Sci 20:157–161. doi:10.1016/S0165-6147(99)01301-2

    Article  CAS  PubMed  Google Scholar 

  • Tessier PA, Naccache PH, Clark-Lewis I, Gladue RP, Neote KS, McColl SR (1997) Chemokine networks in vivo: involvement of C-X-C and C-C chemokines in neutrophil extravasation in vivo in response to TNF-alpha. J Immunol (Baltimore, Md : 1950) 159:3595–3602

    CAS  PubMed  Google Scholar 

  • Uysal HY et al (2012) Preventive effect of dexmedetomidine in ischemia-reperfusion injury. J Craniofac Surg 23:1287–1291. doi:10.1097/SCS.0b013e3182519f24

    Article  PubMed  Google Scholar 

  • Wang Q, Tang XN, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184:53–68. doi:10.1016/j.jneuroim.2006.11.014

    Article  CAS  PubMed  Google Scholar 

  • Weston RM, Jones NM, Jarrott B, Callaway JK (2007) Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia: histochemical and myeloperoxidase correlation with temporal changes in brain injury. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 27:100–114. doi:10.1038/sj.jcbfm.9600324

    Article  CAS  Google Scholar 

  • Wu L, Shen F, Lin L, Zhang X, Bruce IC, Xia Q (2006) The neuroprotection conferred by activating the mitochondrial ATP-sensitive K+ channel is mediated by inhibiting the mitochondrial permeability transition pore. Neurosci Lett 402:184–189. doi:10.1016/j.neulet.2006.04.001

    Article  CAS  PubMed  Google Scholar 

  • Xiong L, Zheng Y, Wu M, Hou L, Zhu Z, Zhang X, Lu Z (2003) Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphateSS-regulated potassium channels after focal cerebral ischemia in rats. Anesth Analg 96:233–237

    CAS  PubMed  Google Scholar 

  • Yang Z, Chen Y, Zhang Y, Jiang Y, Fang X, Xu J (2014) Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels. Mol Med Rep 9:843–850. doi:10.3892/mmr.2014.1912

    CAS  PubMed  Google Scholar 

  • Yilmaz G, Granger DN (2010) Leukocyte recruitment and ischemic brain injury. Neruomol Med 12:193–204. doi:10.1007/s12017-009-8074-1

    Article  CAS  Google Scholar 

  • Yu C, Mei XT, Zheng YP, Xu DH (2014) Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Environ Toxicol Pharmacol 37:729–737. doi:10.1016/j.etap.2014.02.011

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z et al (2015) Pre-treatment of a single high-dose of atorvastatin provided cardioprotection in different ischaemia/reperfusion models via activating mitochondrial KATP channel. Eur J Pharmacol 751:89–98. doi:10.1016/j.ejphar.2015.01.036

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Department of Anesthesia, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, No. 2 of Jingba road of Jinshui District, Zhengzhou, 450014, China

    Feng Yuan, Hongguang Fu, Kai Sun, Shubiao Wu & Tieli Dong

Authors
  1. Feng Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongguang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kai Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shubiao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tieli Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tieli Dong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuan, F., Fu, H., Sun, K. et al. Effect of dexmedetomidine on cerebral ischemia-reperfusion rats by activating mitochondrial ATP-sensitive potassium channel. Metab Brain Dis 32, 539–546 (2017). https://doi.org/10.1007/s11011-016-9945-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-016-9945-4

Keywords

Search

Navigation