Abstract 3569: The Effect of Minocycline on the HARM MRI Marker of Blood-CSF Barrier Opening After Transient MCAO in SHR Rats
Introduction. Early blood-CSF barrier opening imaged as gadolinium enhancement of CSF on FLAIR MRI, the Hyperintense Acute Reperfusion Marker (HARM), has been associated with increased plasma MMP-9 in both clinical and experimental stroke [1-2]. In patients, both elevated MMP-9 and HARM have been associated with tPA treatment and hemorrhagic transformation [3-4]. Minocycline is an MMP-9 inhibitor under investigation as an acute stroke therapy . We hypothesized that minocycline would reduce the early HARM signal in SHR rats undergoing 45 minutes of transient right middle cerebral artery occlusion (MCAO) via the intraluminal suture model.
Methods. Twenty-two consecutive male SHR rats with confirmed non-hemorrhagic stroke on 7T/30cm MRI were randomly assigned to receive minocycline (3mg/kg @ 1mg/mL) or saline control intravenously, injected at the time of reperfusion. Gadolinium was injected at 60 minutes post-reperfusion. Outcome FLAIR images were acquired pre-contrast and at 10 minutes post-contrast. Image analysis, performed blinded to treatment assignment, assessed pre-post FLAIR changes for (1) signal intensity of gadolinium enhancement in the ventricles (2) appearance of HARM in the ipsilateral ventricle (3) appearance of parenchymal enhancement within the infarct.
Results. Ipsilateral ventricular HARM was visible in 9 of 11 animals in each group. Parenchymal enhancement was seen in 6 of 11 in each group. Increase in gadolinium enhancement in the ventricle (either total or ipsilateral only) did not significantly differ between the two groups.
Conclusions. We found no evidence that minocycline reduced blood-CSF or blood-brain barrier opening in this model of 45 minutes transient MCAO in SHR rats. Potential effects of minocycline on blood-CSF or blood-brain barrier at later times after minocycline, on MMP-9 levels or in the presence of tPA in this model requires further study.
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Author Disclosures: S. Warach: None. E.C. Henning: None. R.F. Leoni: None. A.L. Arai: None. L.L. Latour: None. A.C. Silva: None.
- © 2012 by American Heart Association, Inc.