Effects of intravesical onabotulinumtoxinA on bladder dysfunction and autonomic dysreflexia after spinal cord injury: role of nerve growth factor
Effects of intravesical onabotulinumtoxinA on bladder dysfunction and autonomic dysreflexia after spinal cord injury: role of nerve growth factor
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DOI：
10.1111/j.1464-410x.2011.010362.x
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发表时间：
2012-02-01
影响因子：
4.5
通讯作者：
Hassouna, Magdy
中科院分区：
文献类型：
--
作者：
Elkelini, Mohamed S.;Bagli, Darius J.;Hassouna, Magdy
目的评价A型肉毒毒素（onabotA）膀胱内注射对阻断T4脊髓横断（SCT）后膀胱测压图（CMG）诱发的自主神经反射异常（AD）反应的意义。材料与方法雌性大鼠分为三组：假手术组；假手术组；仅 SCT 组；以及采用 onabotA 治疗组的 SCT。每组进一步分为两个亚组：AD评估，或通过酶联免疫吸附测定（ELISA）评估神经生长因子（NGF）。T4-SCT后三周，对所有组进行评估。在 CMG 期间和之后测量动脉压和心率。还从膀胱和 T4 根的背根神经节 (DRG) 提取 NGF，并通过 ELISA 进行定量。在onabotA治疗组中，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 min。使用单变量方差分析对数据进行分析，统计显着性设定为P < 0.05。 结果膀胱内注射onabotA治疗组的最大排尿压力和不受抑制的收缩次数显着降低与仅 SCT 组相比。膀胱内注射 onabotA 显着阻断 SCT 后由 CMG 引起的反射障碍反应（高动脉压伴心动过缓）。膀胱内注射 onabotA 还显着降低膀胱和 T4 DRG 段中的 NGF 浓度。结论本研究的结果表明，膀胱内注射 onabotA 可以控制 SCT 后的神经源性逼尿肌过度活动和 AD。这些发现揭示了潜在的益处膀胱内onabotA治疗脊髓损伤患者的研究，也为通过微创治疗方式控制AD提供了一种新机制。
OBJECTIVETo assess the significance of onabotulinumtoxinA (onabotA) intravesical administration in blocking autonomic dysreflexia (AD) response induced by cystometrogram (CMG) after T4 spinal cord transection (SCT).MATERIALS AND METHODSFemale 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.RESULTSThe 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.CONCLUSIONSThe 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.