Ahmed Rakib Uddin, Edgerton V Reggie, Li Shuai, Zheng Yong-Ping, Alam Monzurul
Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Department of Neurobiology, University of California, Los Angeles, CA, USA.
Dose Response. 2021 Feb 27;19(1):1559325821998136. doi: 10.1177/1559325821998136. eCollection 2021 Jan-Mar.
Buspirone, widely used as a neuropsychiatric drug, has also shown potentials for motor function recovery of injured spinal cord. However, the optimum dosages of such treatment remain unclear. In this study, we investigated the dose-response of Buspirone treatment on reaching and grasping function in cervical cord injured rats. Seventeen adult Sprague-Dawley rats were trained to reach and grasp sugar pellets before a C4 bilateral dorsal column crush injury. After 1 week post-injury, the rats were divided into 3 groups to receive 1 of 3 different dosages of Buspirone (i.p., 1 dose/day: 1.5, n = 5; 2.5, n = 6 and 3.5 mg/kg b.w., n = 6). Forelimb reaching and grip strength test were recorded once per week, within 1 hour of Buspirone administration for 11 weeks post-injury. Different dose groups began to exhibit differences in reaching scores from 4 weeks post-injury. From 4-11 weeks post-injury, the reaching scores were highest in the lowest-dose group rats compared to the other 2 dose groups rats. Average grip strength was also found higher in the lowest-dose rats. Our results demonstrate a significant dose-dependence of Buspirone on the recovery of forelimb motor functions after cervical cord injury with the best performance occurring at the lowest dose tested.
丁螺环酮作为一种广泛使用的神经精神药物,也显示出对脊髓损伤后运动功能恢复的潜力。然而,这种治疗的最佳剂量仍不清楚。在本研究中,我们调查了丁螺环酮治疗对颈髓损伤大鼠抓握功能的剂量反应。17只成年Sprague-Dawley大鼠在C4双侧背柱挤压损伤前接受抓握糖丸训练。损伤后1周,将大鼠分为3组,分别接受3种不同剂量的丁螺环酮(腹腔注射,每天1次:1.5、2.5和3.5mg/kg体重,每组分别为5只、6只和6只)。在损伤后11周内,每周在给予丁螺环酮后1小时内记录一次前肢抓握和握力测试。不同剂量组在损伤后4周开始在抓握分数上表现出差异。在损伤后4-11周,最低剂量组大鼠的抓握分数高于其他两个剂量组大鼠。最低剂量组大鼠的平均握力也更高。我们的结果表明,丁螺环酮对颈髓损伤后前肢运动功能的恢复具有显著的剂量依赖性,在测试的最低剂量下表现最佳。