Preservation of Tropomyosin-Related Kinase B (TrkB) Signaling by Sodium Orthovanadate Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats
Preservation of Tropomyosin-Related Kinase B (TrkB) Signaling by Sodium Orthovanadate Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats
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DOI：
10.1161/strokeaha.110.597344
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发表时间：
2011-02-01
期刊：
影响因子：
8.3
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
--
作者：
Hasegawa, Yu;Suzuki, Hidenori;Zhang, John H.
背景和目的：最近的研究表明，细胞凋亡参与了蛛网膜下腔出血（SAH）后早期脑损伤的发病机制。本研究的目的是研究是否原钒酸钠（SOV）防止后SAH细胞凋亡通过调节生长因子及其下游受体酪氨酸kinases. Method大鼠进行了手术与血管内穿孔模型。用媒介物、3 mg/kg和10 mg/kg SOV处理SAH动物，并评价神经功能和脑水肿。通过Western印迹分析检测了生长因子如成熟脑源性神经营养因子、胰岛素样生长因子-1和血管内皮生长因子的表达以及原肌球蛋白相关激酶B的磷酸化，原肌球蛋白相关激酶B是脑源性神经营养因子的受体酪氨酸激酶，是抗凋亡的下游途径。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染色测量神经元细胞死亡。我们还给予K252 a，原肌球蛋白相关的激酶B拮抗剂，研究神经保护作用的SOV的机制。SOV增加成熟的脑源性神经营养因子，阻止SAH后原肌球蛋白相关激酶B失活和caspase-3激活，导致皮质和海马CA 1区神经元细胞死亡减少。预先注射K252 a取消了SOV的有益作用。结论-目前的研究表明，脑源性神经营养因子诱导的原肌球蛋白相关激酶B激活SOV是必要的，以防止SAH后早期脑损伤。（中风。2011; 42：477-483）。
Background and Purpose-Recent studies reported that apoptosis was involved in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). The aim of this study was to examine whether sodium orthovanadate (SOV) prevents post-SAH apoptosis by modulating growth factors and its downstream receptor tyrosine kinases.Method-Rats were operated on with the endovascular perforation model. SAH animals were treated with vehicle, 3 mg/kg and 10 mg/kg SOV, and evaluated regarding neurofunction and brain edema. The expression of growth factors such as mature brain-derived neurotrophic factor, insulin-like growth factor-1, and vascular endothelial growth factor and phosphorylation of tropomyosin-related kinase B, which is a receptor tyrosine kinase for brain-derived neurotrophic factor and the downstream pathway in antiapoptosis, was examined by Western blot analysis. Neuronal cell death was measured with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. We also administered K252a, a tropomyosin-related kinase B antagonist, to examine the mechanisms for neuroprotective effects by SOV.Results-SOV significantly improved neurofunction and reduced brain edema after SAH. SOV increased mature brain-derived neurotrophic factor and prevented post-SAH tropomyosin-related kinase B inactivation and caspase-3 activation, resulting in attenuation of neuronal cell death in the cortex and hippocampal CA1 region. Preinjection of K252a abolished the beneficial effects of SOV.Conclusions-The current study showed that brain-derived neurotrophic factor-induced tropomyosin-related kinase B activation by SOV was necessary for protection against early brain injury after SAH. (Stroke. 2011; 42: 477-483.)