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MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury.
- J M Simard, P G Popovich, O Tsymbalyuk, J Caridi, R P Gullapalli, M J Kilbourne, and V Gerzanich.
- 1] Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA [2] Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA [3] Department of Physiology, University of Maryland School of Medicine, Baltimore MD, USA.
- Spinal Cord. 2013 Nov 1; 51 (11): 823-7.
Study DesignExperimental, controlled, animal study.ObjectivesTo use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion.SettingBaltimore.MethodsAdult female Long-Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide).ResultsMRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (P<0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P>0.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (P<0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated with significantly better neurological function (unilateral BBB scores) at 24 h in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral (median scores, 12 vs 2; P<0.001) hindlimbs.ConclusionMRI is an accurate non-invasive imaging biomarker of lesion expansion and is a sensitive measure of the ability of glibenclamide to reduce lesion expansion.
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