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• Original Article •
Spatiotemporal evolution of blood brain barrier damage associated with changes of brain metabolites following ischemia onset
ZHANG Tao  NIE Ting-ting  JIA Yan-long  YI Mei-zhi  DAI Zhuo-zhi  YAN Gen  WU Ren-hua 

DOI:10.3969/j.issn.1674-8034.2014.05.014.


[Abstract] 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 contrast-enhanced 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-T1WI 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 efficacy of early thrombolytic therapy.
[Keywords] Blood brain barrier；Magnetic resonance spectroscopy；Contrast enhanced T1WI；Ischemia stroke

ZHANG Tao Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

NIE Ting-ting Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

JIA Yan-long Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

YI Mei-zhi Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

DAI Zhuo-zhi Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

YAN Gen Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China

WU Ren-hua * Department of Medical Imaging, 2nd Affilicated Hospital, Shantou University Medical College, Shantou 515041, China; Provincial Key Laboratory of Medical Molecular Imaging, Guangdong, Medical College of Shantou University, Shantou 515041, China

*Correspondence to: Wu RH, E-mail: cjr.wurenhua@vip.163.com

Conflicts of interest   None.

Received  2014-05-26
Accepted  2014-07-20
DOI: 10.3969/j.issn.1674-8034.2014.05.014
DOI:10.3969/j.issn.1674-8034.2014.05.014.

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