[Orexin-A promotes motor function recovery of rats with spinal cord injury by regulating ionotropic glutamate receptors].

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2025-05-20 DOI:10.12122/j.issn.1673-4254.2025.05.15

Guanglü He, Wanyu Chu, Yan Li, Xin Sheng, Hao Luo, Aiping Xu, Mingjie Bian, Huanhuan Zhang, Mengya Wang, Chao Zheng

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引用次数: 0

Abstract

Objectives: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI).

Methods: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion.

Results: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats.

Conclusions: Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.

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[食欲素a通过调节嗜离子性谷氨酸受体促进脊髓损伤大鼠运动功能恢复]。

目的：探讨食欲素a介导的嗜离子性谷氨酸受体调控对脊髓损伤大鼠运动功能恢复的促进作用。方法：将36只新生SD大鼠（7 ~ 14日龄）随机分为6组（n=6），包括正常对照组、假手术组和4个SCI组，在PCI术后连续3 d每日鞘内注射生理盐水、DNQX、食欲素- a或食欲素- a +DNQX。用血脑屏障（BBB）评分和斜面试验评价脊髓损伤前1天、后1、3、7天大鼠的运动功能。膜片钳实验，制备对照组、假手术组、SCI组和SCI+食欲素组新生大鼠脊髓切片，急性分离腹角神经元，测定谷氨酸灌注下谷氨酸受体介导电流的逆转电位和动态指标。结果：在脊髓损伤后3和7天，orexin- a治疗的大鼠BBB评分和握力倾斜角度明显高于其他干预组。与单用DNQX治疗的大鼠相比，食欲素与DNQX联合治疗的大鼠在PCI术后第7天BBB评分和握力倾斜角度均显著升高。在膜片钳实验中，与假手术和食欲素处理大鼠相比，脊髓损伤大鼠腹角神经元表现出更高的逆转电位和更大的谷氨酸电流上升斜率和更短的衰减时间。结论：食欲素a促进脊髓损伤大鼠运动功能恢复可能是通过改善嗜离子性谷氨酸受体的功能来实现的。

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