title: Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: From the Department of Radiology and the Research Institute of Radiological Science (S.S.A., D.J.K., J.K., N.-Y.S., S.-K.L.).
authors.forename: S S
authors.initials: SS
authors.lastname: Ahn
authors.affiliation: Department of Pathology (S.H.K.), Brain Research Institute.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Anatomy (J.E.L.), Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Radiology (K.J.A., H.S.C.), The Catholic University College of Medicine, Seoul, Seoul, Republic of Korea.
authors.forename: K J
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: From the Department of Radiology and the Research Institute of Radiological Science (S.S.A., D.J.K., J.K., N.-Y.S., S.-K.L.).
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Radiology (K.J.A., H.S.C.), The Catholic University College of Medicine, Seoul, Seoul, Republic of Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Choi
authors.affiliation: From the Department of Radiology and the Research Institute of Radiological Science (S.S.A., D.J.K., J.K., N.-Y.S., S.-K.L.).
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: From the Department of Radiology and the Research Institute of Radiological Science (S.S.A., D.J.K., J.K., N.-Y.S., S.-K.L.).
authors.forename: N-Y
authors.initials: NY
authors.lastname: Shin
authors.affiliation: From the Department of Radiology and the Research Institute of Radiological Science (S.S.A., D.J.K., J.K., N.-Y.S., S.-K.L.) slee@yuhs.ac lee.seungkoo@gmail.com.
authors.forename: S-K
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000376:Agmatine