Spinal cord injury with unilateral versus bilateral primary hemorrhage--effects of glibenclamide

In spinal cord injury (SCI), block of Sur1-regulated NC(Ca-ATP) channels by glibenclamide protects penumbral capillaries from delayed fragmentation, resulting in reduced secondary hemorrhage, smaller lesions and better neurological function. All published experiments demonstrating a beneficial effect of glibenclamide in rat models of SCI have used a cervical hemicord impact calibrated to produce primary hemorrhage located exclusively ipsilateral to the site of impact. Here, we tested the hypothesis that glibenclamide also would be protective in a model with more extensive, bilateral primary hemorrhage. We studied the effect of glibenclamide in 2 rat cervical hemicord contusion models with identical impact force (10 g, 25 mm), one with the impactor positioned laterally to yield unilateral primary hemorrhage (UPH), and the other with the impactor positioned more medially, yielding larger, bilateral primary hemorrhages (BPH) and 6-week lesion volumes that were 45% larger. Functional outcome measures included: modified (unilateral) Basso, Beattie, and Bresnahan scores, angled plane performance, and rearing times. In the UPH model, the effects of glibenclamide were similar to previous observations, including a functional benefit as early as 24h after injury and 6-week lesion volumes that were 57% smaller than controls. In the BPH model, glibenclamide exerted a significant benefit over controls, but the functional benefit was smaller than in the UPH model and 6-week lesion volumes were 33% smaller than controls. We conclude that glibenclamide is beneficial in different models of cervical SCI, with the magnitude of the benefit depending on the magnitude and extent of primary hemorrhage.