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Endothelin-1 Induced Middle Cerebral Artery Occlusion Model for Ischemic Stroke with Laser Doppler Flowmetry Guidance in Rat
Published on: February 16, 2013
Laser Doppler flowmetry predicts occlusion but not tPA-mediated reperfusion success after rat embolic stroke
Nils Henninger1, James Bouley, Bernt T Bråtane
1Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. nils.henninger@umassmed.edu
Background And Purpose:
Laser Doppler flowmetry (LDF) is increasingly used to assess adequate occlusion after embolic stroke (ES) in rats.
Methods:
Employing LDF, relative regional cerebral blood flow (rCBF) was continuously monitored during the first 2 h following ES and correlated with 24 h 2,3,5-triphenyltetrazolium chloride (TTC)-staining of corrected infarct volume. In a preliminary experiment (n=18), it was demonstrated that rCBF-reduction to 37% or less of baseline correctly identified occlusion success in the suture middle cerebral artery occlusion (sMCAO) model. Using the same methodology, we then assessed whether LDF allowed for identification of animals with successful ES (experiment 2, n=26) and tissue plasminogen activator (tPA)-mediated reperfusion following ES (experiment 3, n=28).
Results:
In ES rats, 3 infarct patterns were identified: small (<150 mm(3)), medium ( approximately 250 mm(3)), and large (>400 mm(3)). Rats with an rCBF below 45% of preocclusion values had an 80% probability of developing medium to large infarcts, whereas rats with an rCBF above the 45%-threshold had a 100% chance of developing small infarcts. LDF did not reliably detect reperfusion in tPA-treated animals (sensitivity=40%), because it apparently occurred within brain areas remote from the LDF-monitoring site as indicated by TTC-staining and magnetic resonance angiography in a subset of animals.
Conclusion:
LDF is an excellent screening method to identify animals with successful ES; however, distinction of medium from large infarcts is not possible, the critical threshold for identifying adequate occlusion is higher than in the sMCAO model, and LDF poorly predicts tPA-mediated reperfusion.
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