1 Department of Anatomy, Université du Québec à Trois-Rivières (UQTR) , Québec, Canada .
2 CogNAC Research Group, Université du Québec à Trois-Rivières (UQTR) , Québec, Canada .
J Neurotrauma. 2018 Sep 15;35(18):2208-2221. doi: 10.1089/neu.2017.5476. Epub 2018 May 7.
Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional recovery with multi-targeted therapy combining pharmacological treatment and training, consistent improvements in locomotor control by descending transmission or spinal network facilitation are still eluding clinicians and researchers. Lately, United States Food and Drug Administration-approved buspirone has shown promise and promoted locomotor-like movement occurrence in SCL patients, but evidence on how and where it exerts its effects is lacking. The objective of the present study was, first, to verify buspirone effect on locomotor spinal network and to evaluate if it promoted functional recovery when combined with training. Also, we evaluated buspirone impact on locomotion in mice that had recovered from a previous hemisection before sustaining the spinal transection. This dual lesion paradigm has allowed confirmation of spinal network involvement in recovery after an incomplete SCL. Buspirone acutely increased the number of steps taken, the coupling strength between hindlimbs, angular excursion of the hip joint during locomotion, and improved paw positioning at contact and paw drag (ps < 0.05). Moreover, it induced long-lasting improvements of paw positioning at contact and paw drag when combined with training in mice after a dual lesion paradigm. Altogether, the results indicate that buspirone exerts considerable acute facilitation of spinally mediated locomotion, and could be used in combination with training to promote functional recovery after SCL.
尽管人们努力通过结合药物治疗和训练的多靶点治疗来增强脊髓损伤 (SCL) 患者的功能恢复,但通过下行传输或脊髓网络促进来改善运动控制的一致改善仍然让临床医生和研究人员感到困惑。最近,美国食品和药物管理局批准的丁螺环酮显示出了希望,并促进了 SCL 患者类似运动的发生,但缺乏关于它如何以及在何处发挥作用的证据。本研究的目的首先是验证丁螺环酮对运动性脊髓网络的影响,并评估其与训练结合时是否促进功能恢复。此外,我们还评估了丁螺环酮对先前半横切后恢复的小鼠的运动的影响。这种双重损伤范式允许确认不完全 SCL 后恢复过程中脊髓网络的参与。丁螺环酮急性增加了行走的步数、后肢之间的耦合强度、运动时髋关节的角度偏移,并且改善了接触时的足部定位和足部拖拽(p<0.05)。此外,当与双重损伤范式后接受训练的小鼠结合使用时,它可以长期改善接触时的足部定位和足部拖拽。总之,结果表明丁螺环酮对脊髓介导的运动具有相当大的急性促进作用,并可与训练结合使用,以促进 SCL 后的功能恢复。