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首页> 外文期刊>Experimental Neurology >Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury
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Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury

机译：独立评估格列本脲对减轻颈脊髓损伤后进行性出血性坏死的作用

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These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence - Spinal Cord Injury (FORE-SCI) - Replication". Our goal was to replicate pre-clinical data from Simard et al. (2007) showing that glibenclamide, an FDA approved anti-diabetic drug that targets sulfonylurea receptor 1 (SUR1)-regulated Ca 2+ activated, [ATP] i-sensitive nonspecific cation channels, attenuates secondary intraspinal hemorrhage and secondary neurodegeneration caused by hemicontusion injury in rat cervical spinal cord. In an initial replication attempt, the Infinite Horizons impactor was used to deliver a standard unilateral contusion injury near the spinal cord midline. Glibenclamide was administered continuously via osmotic pump beginning immediately post-SCI. The ability of glibenclamide to limit intraspinal hemorrhage was analyzed at 6, 12 and 24h post-injury using a colorimetric assay. Acute recovery (24h) of forelimb function was also assessed. Analysis of data from these initial studies revealed no difference between glibenclamide and vehicle-treated SCI rats. Later, it was determined that differences in primary trauma affect the efficacy of glibenclamide. Indeed, the magnitude and distribution of primary intraspinal hemorrhage was greater when the impact was directed to the dorsomedial region of the cervical hemicord (as in our initial replication experiment), as compared to the dorsolateral spinal cord (as in the Simard et al. experiment). In three subsequent experiments, injury was directed to the dorsolateral spinal cord. In each case, glibenclamide reduced post-traumatic hemorrhage 24-48h post-injury. In the third experiment, we also assessed function and found that acute reduction of hemorrhage led to improved functional recovery. Thus, independent replication of the Simard et al. data was achieved. These data illustrate that the injury model and type of trauma can determine the efficacy of pre-clinical pharmacological treatments after SCI.
机译：这些实验是作为NIH-NINDS合同的一部分完成的，该合同的标题为“卓越研究设施-脊髓损伤（FORE-SCI）-复制”。我们的目标是复制Simard等人的临床前数据。 （2007年）表明，格列本脲是FDA批准的抗糖尿病药物，其靶向磺酰脲受体1（SUR1）调节的Ca 2+激活的[ATP] i敏感非特异性阳离子通道，可减轻由半胱氨酸损伤引起的继发性脊髓内出血和继发性神经变性。在大鼠颈脊髓中。在最初的复制尝试中，Infinite Horizo​​ns撞击器用于在脊髓中线附近进行标准的单侧挫伤损伤。 SCI后立即开始通过渗透泵连续给予格列本脲。使用比色测定法分析了损伤后第6、12和24小时的格列本脲限制脊髓内出血的能力。还评估了前肢功能的急性恢复（24小时）。这些初步研究的数据分析表明，格列本脲和用载体治疗的SCI大鼠之间没有差异。后来，确定原发性创伤的差异会影响格列本脲的疗效。实际上，与后外侧脊髓相比（如Simard等人的实验），当冲击直接作用于子宫颈半球的背部区域时（如我们最初的复制实验），原发性脊柱内出血的幅度和分布会更大。 ）。在随后的三个实验中，损伤直接针对背外侧脊髓。在每种情况下，格列本脲减少了创伤后24-48h的创伤后出血。在第三个实验中，我们还评估了功能，发现出血的急性减少导致功能恢复改善。因此，Simard等人的独立复制。数据已实现。这些数据表明，损伤模型和创伤类型可以确定SCI后临床前药理学治疗的功效。

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