超急性脑卒中血脑屏障和相关脑代谢物变化的研究

Spatiotemporal evolution of blood brain barrier damage associated with changes of brain metabolites following ischemia onset

目的利用高场强MRI序列描绘早期脑卒中血脑屏障(BBB)损伤随时间变化的影像学特征,并结合频谱中脑代谢物的变化情况,为早期溶栓治疗提供直观和个体化的影像学指导信息。材料与方法健康SD大鼠20只,采用栓线法制备大鼠大脑中动脉闭塞(MCAO)模型,在Angilent 7.0 T动物MR扫描仪上行常规扫描(T1WI、T2WI、DWI),静脉注射MRI对比剂Gd-DTPA后行T1WI增强扫描,并利用MR频谱(1H MRS)技术测量超早期各时间段内病灶区的脑代谢物浓度变化,并用LCModel软件定量出病变区特定代谢物的绝对浓度。结果各组MCAO大鼠,大脑中动脉闭塞10 min后,DWI均能在大脑中动脉供血相应纹状体区及顶叶皮层区显示出异常的高信号,其中1.5 h组MCAO大鼠,大脑中动脉闭塞1.5 h再灌注30 min后,增强T1WI扫描出现脑室系统(第三脑室,侧脑室等)明显高信号改变;而2.0 h组MCAO大鼠再灌注30 min后局部脑实质内可出现明显T1高信号改变。未灌注组MCAO大鼠频谱发现,大脑中动脉闭塞1 h(频谱第一时间段)病变缺血区较对侧正常区Lac峰明显增高,NAA峰明显下降;谷氨酸和牛磺酸的绝对浓度于2 h内逐渐上升至峰值后,3 h段开始明显下降。结论利用MRI对比剂Gd-DTPA的T1WI成像方法可描绘出急性缺血性脑卒中BBB损伤随时间的变化,并采用MR频谱技术正确量化同时期相关脑代谢物的变化。总之,这些相关评估将对溶栓治疗提供客观和个体化的影像学信息。

Objectives： Blood brain barrier（BBB） damage that occurs within the thrombolytic time window is increasingly appreciated to negatively impact the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. Here, we investigated the topographical distribution of BBB damage and its association with tissue injury within the first 3 h after ischemia onset and the related roles of neurochemical metabolites profiles in this process. Materials and Methods： Here, using contrastenhanced magnetic resonance imaging（CE-MRI） and single-voxel localization technique, we assessed BBB disruption onset time and related neurochemical alteration in rats following middle cerebral artery occlusion（MCAO） for 1, 2 and 3 h. Proton metabolites were quantified using LCModel software. Results： In the 1.5 h MCAO group, after 0.5 h reperfusion, abnormal hyperintense signals were seen in both lateral ventricles and the central canal in the CE-T1 WI image, and expanded with time to other MCA regions, including the ventromedial striatum in the 2 h MCAO group, after 0.5 h reperfusion. The concentrations of glutamate＋glutamine（Glu＋Gln）, taurine（Tau） and creatine＋phosphocreatine（Cr＋PCr） increased gradually within the first 2 h（P〈0.05, respectively）, and then decreased（P〈0.05, respectively） in the following 1 h after ischemia onset, as evaluated by 1H-MRS. Other metabolites observed in this study did not show significant changes over the time. Conclusions： Our findings suggest Tau, Glu＋Gln and Cr＋PCr levels may be useful biomarkers to detect BBB damage and relevant events in the ischemic cascade, and predict onset time of BBB disruption to improve the accuracy of acute stroke diagnosis and determine the safety and effi cacy of early thrombolytic therapy.