Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats
Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats
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DOI：
10.1097/01.ju.0000088340.26588.74
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发表时间：
2004-01-01
影响因子：
6.6
通讯作者：
Yoshimura, N
中科院分区：
文献类型：
--
作者：
Seki, S;Sasaki, K;Yoshimura, N
目的：探讨神经生长因子（NGF）抗体（NGF- abs）鞘内应用和辣椒素处理c纤维传入通路脱敏对脊髓损伤后逼尿肌-括约肌协同障碍（DSD）的影响。材料与方法：采用Th8 ~ th9时全断脊髓诱导成年雌性大鼠脊髓损伤。脊髓化后10天，通过插入鞘内导管连接渗透泵，在L6-S1脊髓水平连续给药NGF-Ab（每天10杯）2周。另一组大鼠在去棘后3周和实验前5天皮下注射辣椒素125 mg/kg。同时记录膀胱内压和尿道灌注压。用酶联免疫吸附法测定脊髓大鼠L6脊髓NGF水平。结果：各组大鼠均出现DSD。神经生长因子- ab和辣椒素处理的脊髓化大鼠在膀胱收缩高峰时的平均尿道压力增幅分别比对照大鼠低84%和78%。经NGF- ab处理后，L6脊髓NGF水平比载药处理大鼠显著降低38%，其中L6脊髓NGF水平比脊髓完整大鼠高7倍。结论：脊髓中NGF水平的升高可能导致脊髓损伤后DSD的出现，至少部分是由c纤维膀胱传入神经介导的。因此，抑制传入通路中的NGF水平可能有助于治疗脊髓损伤后的DSD。
Purpose: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (NGF-Abs) and desensitization of C-fiber afferent pathways by capsaicin treatment on detrusor-sphincter dyssynergia (DSD) after spinal cord injury (SCI).Materials and Methods: In adult female rats SCI was induced by complete transection of the spinal cord at Th8 to 9. Ten days after spinalization vehicle or NGF-Ab (10 mug daily) was continuously administered at the level of the L6-S1 spinal cord through an implanted intrathecal catheter connected to an osmotic pump for 2 weeks. Another group of spinalized rats was treated with capsaicin (125 mg/kg subcutaneously) 3 weeks after spinalization and 5 days before experiments. Simultaneous recordings of intravesical pressure and urethral perfusion pressure were then performed. NGF levels in the L6 spinal cord were measured in vehicle or NGF-Ab treated spinalized rats using enzyme-linked immunosorbent assay.Results: DSD was observed in all vehicle treated spinalized rats. The average urethral pressure increase at the peak bladder contraction was significantly lower by 84% and 78% in NGF-Ab and capsaicin treated spinalized rats, respectively, than in vehicle treated rats. After NGF-Ab treatment NGF levels were significantly decreased by 38% in the L6 spinal cord compared with vehicle treated spinalized rats, in which NGF levels in the L6 spinal cord were 7 times higher than in spinal intact rats.Conclusions: Increased levels of NGF in the spinal cord could contribute to the emergence of DSD that is at least in part mediated by C-fiber bladder afferents after SCI. Thus suppression of NGF levels in afferent pathways could be useful for treating DSD following SCI.