Advances in Clinical and Experimental Medicine
2020, vol. 29, nr 6, June, p. 695–700
Publication type: original article
Isoflurane cerebral preconditioning in a spontaneous hypertension rat model is associated with sphingosine kinases
1 Department of Surgery, First Affiliated Hospital of Soochow University, Suzhou, China
2 Medical College, Soochow University, Suzhou, China
3 Department of Nephrology, First Affiliated Hospital of Soochow University, Suzhou, China
Background. Isoflurane preconditioning could reduce different kinds of brain injury via sphingosine kinase (SPK). Both sphingosine kinase 1 and sphingosine kinase 2 play important roles in brain protection. However, the effects of isoflurane preconditioning on SPK expression in hypertension have not been investigated before.
Objectives. To verify whether the neuroprotective effects of the anesthetic isoflurane after an ischemic injury are altered in hypertension and to identify its possible mechanisms involving SPK.
Material and Methods. Wistar rats (control) and spontaneous hypertension rats (SHR) were exposed to isoflurane preconditioning before transient middle cerebral artery occlusion. The infarct volumes of cortical and subcortical brain areas were measured. The expression levels of SPK1 and SPK2 were measured before and after isoflurane preconditioning.
Results. In the SHR group, isoflurane preconditioning significantly reduced only the infarct volumes of the subcortical brain (p < 0.05), not of the cortical brain. After 3 h of isoflurane exposure and preconditioning, SPK2 levels in the SHR group increased in the cortical brain (p < 0.05), but not in the subcortical brain area, Unlike in the control group, isoflurane exposure and preconditioning could significantly increase SPK2 levels in both cortical and subcortical brain area.
Conclusion. The brain protection effects induced by isoflurane preconditioning after an ischemic injury are mainly mediated by the SPK2 isoform and are somewhat impaired in hypertension. Attention should be paid to ischemic injury patients with hypertension.
cerebral preconditioning, isoflurane, hypertension, brain ischemic injury
- Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: From experimental strategies to clinical use. Lancet Neurol. 2009;8(4):398–412.
- Gidday, JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006;7(6):437–448.
- Zheng, S, Zuo Z. Isoflurane preconditioning induces neuroprotection against ischemia via activation of P38 mitogen-activated protein kinases. Mol Pharmacol. 2004;65(5):1172–1180.
- Harada J, Foley M, Michael M, Waeber C. Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J Neurochem. 2004;88(4):1026–1039.
- Zhou Y, Lekic T, Fathali N, et al. Isoflurane posttreatment reduces neonatal hypoxic-ischemic brain injury in rats by the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway. Stroke. 2010;41(7):1521–1527.
- Altray O, Yu H, Sherchan P, et al. Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice. Crit Care Med. 2012;40(6):1908–1913.
- Yu H, Suzuki H, Takumi S, Rolland W, Zhang JH. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke. 2010;41(2):368–374.
- Wei Y, Yemisci M, Kim HH, et al. Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol. 2011;69(1):119–129.
- Ming YL, Ying W, Tao Q, Wang Y, Smith C, Waeber C. Sphingosine kinase 2 mediates cerebral preconditioning and protects the mouse brain against ischemic injury. Stroke. 2012;43(1):199–204.
- Izumi Y, Roussel S, Pinard E, Seylaz J. Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 1991;11(6):1025–1030.
- O’Donnell ME, Lien T, Lam T, Liu X, Anderson SE. Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke. J Cereb Blood Flow Metab. 2004;24(9):1046–1056.
- Bryan L, Kordula T, Spiegel S, Milstein S. Regulation and functions of sphingosine kinases in the brain. Biochim Biophys Acta. 2008;1781(9):459–466.
- Wacker BK, Park TS, Gidday JM. Hypoxic preconditioning-induced cerebral ischemic tolerance: Role of microvascular sphingosine kinase 2. Stroke. 2009;40(10):3342–3348.
- Graler MH, Goetzl EJ. The immunosuppressant FTY720 downregulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J. 2004;18(3):551–553.
- Kluk MJ, Hla T. Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta. 2002;1582(1–3):72–80.
- Wang FH, Nobes C, Hall A, Spiegel S. Sphingosine 1-phosphate stimulates rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 fibroblasts. Biochem J. 1997;324(Pt 2):481–488.
- Yogi A, Glaucia EC, Anna BA, et al. Sphingosine-1-phosphate-induced inflammation involves receptor tyrosine kinase transactivation in vascular cells: Upregulation in hypertension. Hypertension. 2011;57(4):809–818.
- Grey A, Xu X, Hill B, et al. Osteoblastic cells express phospholipid receptors and phosphatases and proliferate in response to sphingosine-1-phosphate. Calcif Tissue Int. 2004;74(6):542–550.
- Song DD, Zhang TT, Chen JL, et al. Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain. Cell Death Dis. 2017;8(7):e2912.
- Varol F, Uzunoglu R, Erbas H, Süt N, Sayın C. VEGFR-1, Bcl-2, and HO-1 ratios in pregnant women with hypertension. Clin Appl Thromb Hemost. 2015;21(3):285–288.
- Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology. 2011;76(8 Suppl 3):S3–S8.