A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury.
A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury.
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DOI：
10.1089/neu.2015.3892
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发表时间：
2015-11-01
影响因子：
4.2
通讯作者：
Simard JM
中科院分区：
文献类型：
--
作者：
Hosier H;Peterson D;Tsymbalyuk O;Keledjian K;Smith BR;Ivanova S;Gerzanich V;Popovich PG;Simard JM
最近的临床前研究已经确定了三种特别有希望减少创伤性脊髓损伤（SCI）后急性病变扩展的治疗方法：利鲁唑、全身低温和格列本脲。每一种都在多个独立重复的研究中证明了疗效，但由于使用了不同的模型，涉及了不同的实验室，评估了不同的结果，因此无法对它们的疗效或安全性进行比较。在这里，我们使用下颈半脊髓挫伤模型，比较三种治疗方法的安全性和有效性，从创伤后4小时开始给药。对照组、利鲁唑组、低温组和格列苯脲组的治疗相关死亡率分别为30%（3/10）、30%（3/10）、12.5%（1/8）和0%（0/7）。对于幸存者来说，与对照组相比，所有三种治疗方法均显示出良好的总体疗效。在野外运动评分（修改Basso， Beattie和Bresnahan评分）上，低温治疗和格列苯脲治疗的动物在整个研究过程中基本上没有区别，而利鲁唑治疗的大鼠在前两周表现不佳；在最后四周，三种治疗方法的得分相似，与对照组有显著差异。在平衡性方面，低温和格列本脲治疗明显优于利鲁唑。创伤后，格列本脲组的大鼠迅速恢复了正常的体重增加模式，与其他所有组明显不同。6周时病变体积：对照组、利鲁唑组、低温组和格列苯脲组分别为4.8±0.7、3.5±0.4、3.1±0.3和2.5±0.3 mm3；对剩余脊髓组织的测量证实了这些结果。总体而言，就安全性和有效性而言，全身低温和格列本脲优于利鲁唑。
Recent preclinical studies have identified three treatments that are especially promising for reducing acute lesion expansion following traumatic spinal cord injury (SCI): riluzole, systemic hypothermia, and glibenclamide. Each has demonstrated efficacy in multiple studies with independent replication, but there is no way to compare them in terms of efficacy or safety, since different models were used, different laboratories were involved, and different outcomes were evaluated. Here, using a model of lower cervical hemicord contusion, we compared safety and efficacy for the three treatments, administered beginning 4 h after trauma. Treatment-associated mortality was 30% (3/10), 30% (3/10), 12.5% (1/8), and 0% (0/7) in the control, riluzole, hypothermia, and glibenclamide groups, respectively. For survivors, all three treatments showed overall favorable efficacy, compared with controls. On open-field locomotor scores (modified Basso, Beattie, and Bresnahan scores), hypothermia- and glibenclamide-treated animals were largely indistinguishable throughout the study, whereas riluzole-treated rats underperformed for the first two weeks; during the last four weeks, scores for the three treatments were similar, and significantly different from controls. On beam balance, hypothermia and glibenclamide treatments showed significant advantages over riluzole. After trauma, rats in the glibenclamide group rapidly regained a normal pattern of weight gain that differed markedly and significantly from that in all other groups. Lesion volumes at six weeks were: 4.8±0.7, 3.5±0.4, 3.1±0.3 and 2.5±0.3 mm3 in the control, riluzole, hypothermia, and glibenclamide groups, respectively; measurements of spared spinal cord tissue confirmed these results. Overall, in terms of safety and efficacy, systemic hypothermia and glibenclamide were superior to riluzole.