Abstract
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.
Highlights
Spinal cord injury (SCI) remains one of the foremost unsolved challenges in medicine
In series 1, we evaluated the expansion of the hemorrhagic contusion using serial magnetic resonance imaging (MRI) scans obtained at 1 and 24 h after trauma, with the T2 hypodensity being taken as a measure of extravasated blood.[16,17,18,19]
We considered the hemorrhagic area observed at 15 min to represent the primary hemorrhage due to the trauma and the hemorrhagic area observed at 24 h to represent the primary hemorrhage plus the secondary hemorrhage, the latter attributable to progressive hemorrhagic necrosis
Summary
Spinal cord injury (SCI) remains one of the foremost unsolved challenges in medicine. The incidence of SCI ranges from 10 to 83 per million people per year, with half of these patients suffering a complete lesion and one-third becoming tetraplegic.[1] At present, little can be done to undo or repair the initial damage to spinal cord tissues, but great hope lies in reducing secondary injury processes triggered by the primary injury that increase the damage and worsen clinical outcome. During the hours after a blunt impact, a dynamic process ensues wherein a hemorrhagic contusion slowly enlarges, resulting in the progressive autodestruction of spinal cord tissues.[2,3,4] Discrete petechial hemorrhages appear, first around the site of injury and in more distant areas.[5] As petechial hemorrhages form and coalesce, the lesion gradually expands, with a characteristic region of hemorrhage that ‘caps’ the advancing front of the lesion. The advancing hemorrhage results from delayed progressive catastrophic failure of the structural integrity of capillaries, a phenomenon termed ‘progressive hemorrhagic necrosis’.2–4
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