Evaluation of riluzole therapy using the glutamate segmental infusion model. - Development of pharmacologic spinal cord protection for amyotrophic lateral screlosis (ALS) -

肌萎缩侧索硬化症(ALS)是一种进行性运动神经元病，目前尚无适当的治疗方法。在临床前瞻性对照研究中，抗谷氨酸剂利鲁唑被报道能延缓ALS的进展。采用节段性谷氨酸灌流模型，观察利鲁唑和AMPA/海人藻酸受体拮抗剂NBQX对脊髓的保护作用。方法：选用体重3.5~4.0 kg的新西兰大白兔，行肾下隔离。A组(n=7)，术前10天口服利鲁唑(100 mg/kg/d)。B组(n=7)不喂利鲁唑。将谷氨酸溶液(50 MM)以2ml/min的速度注入离体腹主动脉段，持续5min。C组(n=8)和D组(n=8)给予利鲁唑(100 mg/kg/d)，连续10天。E组(n=8)，不饲喂利鲁唑。D组和E组分别给予NBQX(4 mg/kg)和谷氨酸(50 MM)灌胃5min。C组给予溶媒，随后按相同方法给予谷氨酸灌胃。使用Tarlov系统评估神经状态。结果：神经功能评分A组为3.7±1.6，B组为0.8±0.6。A组动物神经功能恢复情况明显好于B组(p&lt；0.05)。神经功能评分：C组为3.2±0.6，D组为4.1±0.5，E组为2.3±0.7。D组动物的神经功能恢复明显好于C组和E组(p&lt；0.05)。结论：在节段性谷氨酸注入模型中，利鲁唑联合NBQX可促进脊髓恢复。

Amyotrophic lateral screlosis (ALS) is a progressive motor neuron disease for which there is no adequate treatment. The antiglutamate agent riluzole was reported to slow the progression of ALS in clinical prospective controlled study. Using the segmental glutamate infusion model, we evaluated protective effects of riluzole and NBQX, which is an AMPA/kainate antagonist, to spinal cord in vivo. Method; Infrarenal isolation was performed in New Zealand white rabbits (3.5-4.0kg). Group A animals (n=7) were orally treated with riluzole (100mg/kg/day) for ten days before surgery. Group B animals (n=7) were fed without riluzole. Glutamate solution (50mM) was infused to the isolated abdomial aortic segment at a rate of two ml/min for 5 minutes. Group C (n=8) and group D (n=8) animals received riluzole (100mg/kg/day) for ten days. Group E (n=8) animals were fed without riluzole. Group D and group E animals were pretreated with NBQX (4 mg/kg), followed by the infusion of glutamate (50mM) for 5 minutes. Group C animals received vehicle, followed by the glutamate infusion in the same manner. Neurologic status was assessed using the Tarlov system. Results; Neurologic scores in group A, group B were 3.7±1.6 and 0.8±0.6 respectively. Group A animals exhibited better neurologic recovery compared with group B significantly (p<0.05). Neurologic scores in group C, group D, and group E were 3.2±0.6, 4.1±0.5 and 2.3±0.7 respectively. Group D animals exhibited better neurologic recovery compared with group C and group E significantly (p<0.05). Conclusion; Riluzole combined with NBQX can improve spinal cord recovery in the segmental glutamate infusion model.