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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalAmerican Journal of Neuroradiology
Volume36
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

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Agmatine
Transient Ischemic Attack
Blood-Brain Barrier
Permeability
Extracellular Space
Reperfusion
Factor VIII
Control Groups
Stroke
Plasma Volume
Sprague Dawley Rats
Biomarkers
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology

Cite this

Ahn, S. S. ; Kim, S. H. ; Lee, J. E. ; Ahn, K. J. ; Kim, D. J. ; Choi, H. S. ; Kim, J. ; Shin, N. Y. ; Lee, S. K. / Effects of agmatine on blood-brain barrier stabilization assessed by permeability mri in a rat model of transient cerebral ischemia. In: American Journal of Neuroradiology. 2015 ; Vol. 36, No. 2. pp. 283-288.
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title = "Effects of agmatine on blood-brain barrier stabilization assessed by permeability mri in a rat model of transient cerebral ischemia",
abstract = "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.",
author = "Ahn, {S. S.} and Kim, {S. H.} and Lee, {J. E.} and Ahn, {K. J.} and Kim, {D. J.} and Choi, {H. S.} and J. Kim and Shin, {N. Y.} and Lee, {S. K.}",
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Effects of agmatine on blood-brain barrier stabilization assessed by permeability mri in a rat model of transient cerebral ischemia. / Ahn, S. S.; Kim, S. H.; Lee, J. E.; Ahn, K. J.; Kim, D. J.; Choi, H. S.; Kim, J.; Shin, N. Y.; Lee, S. K.

In: American Journal of Neuroradiology, Vol. 36, No. 2, 01.02.2015, p. 283-288.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of agmatine on blood-brain barrier stabilization assessed by permeability mri in a rat model of transient cerebral ischemia

AU - Ahn, S. S.

AU - Kim, S. H.

AU - Lee, J. E.

AU - Ahn, K. J.

AU - Kim, D. J.

AU - Choi, H. S.

AU - Kim, J.

AU - Shin, N. Y.

AU - Lee, S. K.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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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