Toronto Western Research Institute, University of Toronto, Ontario, Canada.
BJU Int. 2012 Feb;109(3):402-7. doi: 10.1111/j.1464-410X.2011.010362.x. Epub 2011 Jul 6.
To assess the significance of onabotulinumtoxinA (onabotA) intravesical administration in blocking autonomic dysreflexia (AD) response induced by cystometrogram (CMG) after T4 spinal cord transection (SCT).
Female rats were stratified into three groups: a sham group; a SCT-only group; and a SCT with onabotA treatment group. Each group was further subdivided into two subgroups: AD assessment, or nerve growth factor (NGF) assessment via enzyme-linked immunosorbent assay (ELISA). Three weeks after T4-SCT, all groups were assessed. Arterial pressure and heart rate were measured during and after CMG. NGF was also extracted from the bladder and the dorsal root ganglia (DRG) of the T4 root and quantified by ELISA. In the onabotA-treated group, 48 h before assessment, onabotA (1 mL, 20 U/mL in saline) was given using a urethral tube and was left indwelling for 30 min. Univariate anova was used to analyse the data and statistical significance was set at P < 0.05.
The maximum voiding pressure and the number of uninhibited contractions were significantly lower in the group treated with intravesical onabotA than in the SCT-only group. Intravesical onabotA significantly blocked the dysreflexia response (high arterial pressure with bradycardia) induced by CMG after SCT. Intravesical onabotA also significantly lowered NGF concentrations in the bladder and the T4 DRG segment.
The results of the present study showed that intravesical onabotA controls neurogenic detrusor overactivity and AD after SCT. The findings shed light on the potential benefits of intravesical onabotA treatment in patients with spinal cord injury, and also provide a novel mechanism for the control of AD via a minimally invasive treatment modality.
评估膀胱内注射肉毒毒素 A（onabotA）在阻断 T4 脊髓横断（SCT）后膀胱测压（CMG）诱发的自主反射异常（AD）反应中的意义。
将雌性大鼠分为三组：假手术组；SCT 组；SCT 加 onabotA 治疗组。每组再分为 AD 评估组或通过酶联免疫吸附试验（ELISA）评估神经生长因子（NGF）评估组。T4-SCT 后 3 周，所有组均进行评估。在 CMG 期间和之后测量动脉压和心率。还通过 ELISA 从膀胱和 T4 神经根的背根神经节（DRG）提取 NGF 并进行定量。在 onabotA 治疗组中，在评估前 48 小时，通过尿道管给予 onabotA（1 mL，20 U/mL 生理盐水），并留置 30 分钟。采用单因素方差分析对数据进行分析，设定 P < 0.05 为统计学显著性差异。
与 SCT 组相比，膀胱内注射 onabotA 治疗组的最大排空压力和无抑制收缩次数明显降低。膀胱内注射 onabotA 显著阻断了 SCT 后 CMG 诱发的反射异常（低血压伴心动过缓）反应。膀胱内注射 onabotA 还显著降低了膀胱和 T4 DRG 节段的 NGF 浓度。
本研究结果表明，膀胱内注射 onabotA 可控制 SCT 后神经原性逼尿肌过度活动和 AD。这些发现为脊髓损伤患者膀胱内注射 onabotA 治疗提供了潜在益处，并为通过微创治疗方式控制 AD 提供了新的机制。
