Isoflurane cerebral preconditioning in a spontaneous hypertension rat model is associated with sphingosine kinases

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. Conclusions.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.