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Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia

 S.S. Ahn  ;  S.H. Kim  ;  J.E. Lee  ;  K.J. Ahn  ;  D.J. Kim  ;  H.S. Choi  ;  J. Kim  ;  N.-Y. Shin  ;  S.-K. Lee 
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Agmatine/pharmacology* ; Animals ; Blood-Brain Barrier/drug effects* ; Blood-Brain Barrier/physiopathology ; Capillary Permeability/drug effects* ; Disease Models, Animal ; Infarction, Middle Cerebral Artery/physiopathology* ; Magnetic Resonance Imaging/methods* ; Male ; Rats ; Rats, Sprague-Dawley
BACKGROUND AND PURPOSE: BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. MATERIALS AND METHODS: Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. RESULTS: Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). CONCLUSIONS: In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of permeability by using dynamic contrast-enhanced MR imaging. Therefore, dynamic contrast-enhanced MR imaging may serve as a potential imaging biomarker for assessing the BBB stabilization properties of pharmacologic agents.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Joon(김동준) ORCID logo https://orcid.org/0000-0002-7035-087X
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Jinna(김진아) ORCID logo https://orcid.org/0000-0002-9978-4356
Shin, Na Young(신나영)
Ahn, Sung Soo(안성수) ORCID logo https://orcid.org/0000-0002-0503-5558
Lee, Seung Koo(이승구) ORCID logo https://orcid.org/0000-0001-5646-4072
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
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