Abstract：
OBJECTIVE: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI.
METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies.
RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding.
CONCLUSIONS: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.
METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies.
RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding.
CONCLUSIONS: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.
摘要：
目的：评价在脊髓损伤（SCI）部位的中心注射肉毒杆菌毒素A（BoNT/A）对胸SCI雌性大鼠下尿路功能恢复的影响。
方法：将24只患有假手术（T8/T9水平的椎板切除术）或SCI（T8/T9;30g压缩5s）的雌性Wistar大鼠分配到Sham-SS（注射5µL盐溶液）中，Sham-BoNT/A（注射15pg/大鼠，相当于7.5单位/千克BoNT/A，在5微升体积中），SCI-SS（受伤并注射生理盐水），SCI-BoNT/A（受伤并注射了BoNT/A），每组N=6。每周对刻板的排尿行为进行评估，后肢伤害感受，运动活动在手术前1周和手术后6周进行。随后，所有组同时接受尿道外括约肌肌电图(EUS-EMG)和膀胱测量(CMG)检查.
结果：T8/T9胸廓水平的压缩SCI显着损害了感觉和机车功能，以及刻板的排尿行为。然而,SCI后注射BoNT/A可改善这些损伤。注射盐水溶液和BoNT/A对在假手术组中评估的相同参数均无明显影响。EUS-EMG和CMG联合评估揭示了下尿路生理学的重要改善，特别是非排尿收缩的频率和EUS爆发活动的特性的降低，表现为有效排尿期间EUS-EMG信号的幅度和爆发电活动的持续时间。
结论：通过将少量BoNT/A直接注射到SCI的震中，可以潜在地减轻SCI引起的感觉和机车功能的严重损害以及刻板的排尿。需要SNARE复合物的神经毒性神经递质释放的减少可能是BoNT/A触发的机制，以减少SCI区域产生的神经毒性和兴奋过度，从而改善排尿相关的脊髓细胞的存活。
方法：将24只患有假手术（T8/T9水平的椎板切除术）或SCI（T8/T9;30g压缩5s）的雌性Wistar大鼠分配到Sham-SS（注射5µL盐溶液）中，Sham-BoNT/A（注射15pg/大鼠，相当于7.5单位/千克BoNT/A，在5微升体积中），SCI-SS（受伤并注射生理盐水），SCI-BoNT/A（受伤并注射了BoNT/A），每组N=6。每周对刻板的排尿行为进行评估，后肢伤害感受，运动活动在手术前1周和手术后6周进行。随后，所有组同时接受尿道外括约肌肌电图(EUS-EMG)和膀胱测量(CMG)检查.
结果：T8/T9胸廓水平的压缩SCI显着损害了感觉和机车功能，以及刻板的排尿行为。然而,SCI后注射BoNT/A可改善这些损伤。注射盐水溶液和BoNT/A对在假手术组中评估的相同参数均无明显影响。EUS-EMG和CMG联合评估揭示了下尿路生理学的重要改善，特别是非排尿收缩的频率和EUS爆发活动的特性的降低，表现为有效排尿期间EUS-EMG信号的幅度和爆发电活动的持续时间。
结论：通过将少量BoNT/A直接注射到SCI的震中，可以潜在地减轻SCI引起的感觉和机车功能的严重损害以及刻板的排尿。需要SNARE复合物的神经毒性神经递质释放的减少可能是BoNT/A触发的机制，以减少SCI区域产生的神经毒性和兴奋过度，从而改善排尿相关的脊髓细胞的存活。
