Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice.
Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice.
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DOI：
10.1097/ccm.0b013e3182474bc1
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发表时间：
2012-06
影响因子：
8.8
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Altay O;Hasegawa Y;Sherchan P;Suzuki H;Khatibi NH;Tang J;Zhang JH
异氟醚是一种挥发性麻醉剂，具有潜在的神经保护作用和抗细胞凋亡作用。我们研究了异氟醚治疗后是否对蛛网膜下腔出血（SAH）后早期脑损伤（EBI）有保护作用，并确定这种作用是否需要鞘氨醇相关通路的激活。体内对照实验室研究。动物研究实验室。179只8周大的CD-1雄性小鼠，体重30至38克。小鼠血管内穿孔诱发SAH。动物随机分配到假手术组、SAH-vehicle组和SAH+2%异氟醚组。在24小时和72小时评估神经行为功能和脑水肿。Western blotting和免疫荧光法检测鞘氨酸激酶（SphK）、磷酸化Akt （p-Akt）和裂解caspase-3的表达。用末端脱氧核苷酸转移酶介导的尿苷5′-三磷酸-生物素缺口末端标记法检测神经元细胞死亡情况。SphK抑制剂DMS或鞘氨醇1磷酸受体抑制剂VPC23019对异氟烷对sah后EBI的保护作用也进行了研究。异氟醚在SAH后24小时显著改善神经行为功能和脑水肿，但在72小时无显著改善。在24小时，异氟醚减轻了皮质神经元细胞的死亡，与SphK1和p-Akt的增加以及cleaved caspase-3的减少有关。异氟醚的有益作用被DMS和VPC23019所抵消。异氟醚通过鞘氨醇相关通路激活等抗凋亡机制延缓sah后EBI的发展，提示其可用于急性动脉瘤手术或干预期间的麻醉。
Isoflurane, a volatile anesthetic agent, has been recognized for its potential neuroprotective properties and has antiapoptotic effects. We examined whether isoflurane posttreatment is protective against early brain injury (EBI) after subarachnoid hemorrhage (SAH) and determined whether this effect needs sphingosine-related pathway activation. Controlled in vivo laboratory study. Animal research laboratory. 179 eight-week-old male CD-1 mice weighing 30 to 38 g. SAH was induced in mice by endovascular perforation. Animals were randomly assigned to sham-operated, SAH-vehicle, and SAH+2% isoflurane. Neurobehavioral function and brain edema were evaluated at 24 and 72 hours. The expression of sphingosine kinase (SphK), phosphorylated Akt (p-Akt) and cleaved caspase-3 was determined by Western blotting and immunofluorescence. Neuronal cell death was examined by terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling staining. Effects of a SphK inhibitor DMS, or a sphingosine 1 phosphate receptor inhibitor VPC23019 on isoflurane’s protective action against post-SAH EBI were also examined. Isoflurane significantly improved neurobehavioral function and brain edema at 24 hours but not 72 hours after SAH. At 24 hours, isoflurane attenuated neuronal cell death in the cortex, associated with an increase in SphK1 and p-Akt, and a decrease in cleaved caspase-3. The beneficial effects of isoflurane were abolished by DMS and VPC23019. Isoflurane posttreatment delays the development of post-SAH EBI through antiapoptotic mechanisms including sphingosine-related pathway activation, implying its use for anesthesia during acute aneurysm surgery or intervention.