He Guanglü, Chu Wanyu, Li Yan, Sheng Xin, Luo Hao, Xu Aiping, Bian Mingjie, Zhang Huanhuan, Wang Mengya, Zheng Chao
Neurobiology Laboratory, 2Psychophysiology Laboratory, 3Cell Electrophysiology Laboratory, Institute of Physiological Sciences, Wannan Medical College, Wuhu 241002, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 May 20;45(5):1023-1030. doi: 10.12122/j.issn.1673-4254.2025.05.15.
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).
Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (=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.
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.
Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
研究食欲素 A 介导的离子型谷氨酸受体调节对促进脊髓损伤(SCI)大鼠运动功能恢复的作用。
将 36 只新生 SD 大鼠(7 - 14 日龄)随机分为 6 组(每组 = 6 只),包括正常对照组、假手术组以及 4 个 SCI 组,SCI 组在脊髓损伤(PCI)后连续 3 天每天鞘内注射生理盐水、DNQX、食欲素 A 或食欲素 A + DNQX。在 SCI 前 1 天以及 SCI 后 1、3 和 7 天,使用血脑屏障(BBB)评分和倾斜平面试验评估大鼠的运动功能。对于膜片钳实验,制备对照组、假手术组、SCI 组和 SCI + 食欲素组新生大鼠的脊髓切片,急性分离腹角神经元,以确定在谷氨酸灌注下谷氨酸受体介导电流的反转电位和动态指标。
在 SCI 后 3 天和 7 天,接受食欲素 A 治疗的大鼠的 BBB 评分和握力倾斜角度显著高于接受其他干预的大鼠。与单独使用 DNQX 治疗的大鼠相比,接受食欲素和 DNQX 联合治疗的大鼠在 PCI 后第 7 天的 BBB 评分和握力倾斜角度显著更高。在膜片钳实验中,SCI 大鼠模型的腹角神经元表现出比假手术组和食欲素治疗组大鼠明显更高的反转电位以及谷氨酸电流更大的上升斜率和更短的衰减时间。
食欲素 A 可能通过改善离子型谷氨酸受体的功能促进 SCI 大鼠的运动功能恢复。