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http://dx.doi.org/10.4062/biomolther.2015.206

Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury  

Wang, Kun (Department of Anesthesiology, Jining No.1 People's Hospital)
Kong, Xiangang (Department of Anesthesiology, Jining No.1 People's Hospital)
Publication Information
Biomolecules & Therapeutics / v.24, no.5, 2016 , pp. 495-500 More about this Journal
Abstract
This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related $K^+$ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1.
Keywords
Isoflurane; Spinal cord ischemic injury; TREK1; Caspase-3; NADH;
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1 Ambrosio, G., Zweier, J., Duilio, C., Kuppusamy, P., Santoro, G., Elia, P., Tritto, I., Cirillo, P., Condorelli, M. and Chiariello, M. (1993) Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J. Biol. Chem. 268, 18532-18541.
2 Chaitanya, G. V. and Babu, P. P. (2008) Activation of calpain, cathepsin-b and caspase-3 during transient focal cerebral ischemia in rat model. Neurochem. Res. 33, 2178-2186.   DOI
3 Coselli, J. S., LeMaire, S. A., de Figueiredo, L. P. and Kirby, R. P. (1997) Paraplegia after thoracoabdominal aortic aneurysm repair: is dissection a risk factor? Ann. Thorac. Surg. 63, 28-35; discussion 35-36.   DOI
4 Dirnagl, U., Becker, K. and Meisel, A. (2009) Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol. 8, 398-412.   DOI
5 Enyedi, P. and Czirjak, G. (2015) Properties, regulation, pharmacology, and functions of the $K_2P$ channel, TRESK. Pflugers Arch. 467, 945-958.   DOI
6 Franks, N. P. and Honore, E. (2004) The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol. Sci. 25, 601-608.   DOI
7 Gruss, M., Bushell, T. J., Bright, D. P., Lieb, W. R., Mathie, A. and Franks, N. P. (2004) Two-pore-domain $K^+$ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol. Pharmacol. 65, 443-452.   DOI
8 Jiruska, P., de Curtis, M. and Jefferys, J. G. (2014) Modern concepts of focal epileptic networks. Int. Rev. Neurobiol. 114, 1-7.   DOI
9 Hanley, P. J., Ray, J., Brandt, U. and Daut, J. (2002) Halothane, isoflurane and sevoflurane inhibit NADH: ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J. Physiol. (Lond.) 544, 687-693.   DOI
10 Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang-Lazdunski, L., Widmann, C., Zanzouri, M. and Romey, G. (2004) TREK-1, a $K^+$ channel involved in neuroprotection and general anesthesia. EMBO J. 23, 2684-2695.   DOI
11 Kitano, H., Kirsch, J. R., Hurn, P. D. and Murphy, S. J. (2007) Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J. Cereb. Blood Flow Metab. 27, 1108-1128.   DOI
12 Kwon, B. K., Tetzlaff, W., Grauer, J. N., Beiner, J. and Vaccaro, A. R. (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J. 4, 451-464.   DOI
13 Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S. and Wang, X. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.   DOI
14 Liu, Y., Xiong, L., Chen, S. and Wang, Q. (2006) Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists. Can. J. Anaesth. 53, 194-201.   DOI
15 Monaco, B. A., Benicio, A., Contreras, I. S., Mingrone, L. E., Ballester, G. and Moreira, L. F. (2007) Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach. Arq. Bras. Cardiol. 88, 291-296.   DOI
16 Mirkovic, K., Palmersheim, J., Lesage, F. and Wickman, K. (2012) Behavioral characterization of mice lacking Trek channels. Front. Behav. Neurosci. 6, 60.
17 Safi, H. J., Winnerkvist, A., Miller, C. C., Iliopoulos, D. C., Reardon, M. J., Espada, R. and Baldwin, J. C. (1998) Effect of extended crossclamp time during thoracoabdominal aortic aneurysm repair. Ann. Thorac. Surg. 66, 1204-1209.   DOI
18 Sang, H., Cao, L., Qiu, P., Xiong, L., Wang, R. and Yan, G. (2006) Isoflurane produces delayed preconditioning against spinal cord ischemic injury via release of free radicals in rabbits. Anesthesiology 105, 953-960.   DOI
19 Shabbir, M., Syed, D. N., Lall, R. K., Khan, M. R. and Mukhtar, H. (2015) Potent Anti-Proliferative, Pro-Apoptotic Activity of the Maytenus Royleanus Extract against Prostate Cancer Cells: Evidence in In-Vitro and In-Vivo Models. PLoS ONE 10, e0119859.   DOI
20 Siegelbaum, S. A., Camardo, J. S. and Kandel, E. R. (1982) Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature 299, 413-417.   DOI
21 Tong, L., Cai, M., Huang, Y., Zhang, H., Su, B., Li, Z. and Dong, H. (2013) Activation of K2P channel-TREK1 mediates the neuroprotection induced by sevoflurane preconditioning. Br. J. Anaesth. 113, 157-167.
22 Tong, L., Cai, M., Huang, Y., Zhang, H., Su, B., Li, Z. and Dong, H. (2014) Activation of K(2)P channel-TREK1 mediates the neuroprotection induced by sevoflurane preconditioning. Br. J. Anaesth. 113, 157-167.   DOI
23 Turrens, J. F. and Boveris, A. (1980) Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem. J. 191, 421-427.   DOI
24 Wakeno-Takahashi, M., Otani, H., Nakao, S., Imamura, H. and Shingu, K. (2005) Isoflurane induces second window of preconditioning through upregulation of inducible nitric oxide synthase in rat heart. Am. J. Physiol. Heart Circ. Physiol. 289, H2585-H2591.   DOI
25 Yang, Q., Dong, H., Deng, J., Wang, Q., Ye, R., Li, X., Hu, S., Dong, H. and Xiong, L. (2011) Sevoflurane preconditioning induces neuroprotection through reactive oxygen species-mediated up-regulation of antioxidant enzymes in rats. Anesth. Analg. 112, 931-937.   DOI
26 Yin, X., Su, B., Zhang, H., Song, W., Wu, H., Chen, X., Zhang, X., Dong, H. and Xiong, L. (2012) TREK1 activation mediates spinal cord ischemic tolerance induced by isoflurane preconditioning in rats. Neurosci. Lett. 515, 115-120.   DOI
27 Zhang, H. P., Yuan, L. B., Zhao, R. N., Tong, L., Ma, R., Dong, H. L. and Xiong, L. (2010) Isoflurane preconditioning induces neuroprotection by attenuating ubiquitin-conjugated protein aggregation in a mouse model of transient global cerebral ischemia. Anesth. Analg. 111, 506-514.   DOI
28 Zheng, S. and Zuo, Z. (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of P38 mitogen-activated protein kinases. Mol. Pharmacol. 65, 1172-1180.   DOI