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Neuro-stem cell transplantation therapy for the neurogenic bladder caused by spinal cord injuries and central nervous system disorders

神经干细胞移植治疗脊髓损伤和中枢神经系统疾病引起的神经源性膀胱

基本信息

批准号：
15591678
负责人：
ISHIZUKA Osamu
金额：
$ 2.24万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In this year, we focused on the precise overactive bladder mechanism before starting neuro-stem cell transplantation. Especially, we focused on neurokinin receptors and ATP. Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP.Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 microM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly increased threshold pressure, voiding interval, micturition volume and bladder c … More apacity. In the vehicle-pretreated rats, intravesical instillation of capsaicin or acetic acid significantly decreased voiding interval, micturition volume, and bladder capacity. However, in the RTX-pretreated rats, neither capsaicin nor acetic acid affected any parameter. On the other hand, intravesical ATP (0.1 mM) significantly decreased voiding interval and micturition volume in both groups of animals. At 1.0 mM, ATP also increased basal pressure and decreased the pressure threshold for micturition in both groups.The present results support the view that increased extracellular ATP has a role in mechano-afferent transduction in the rat bladder and that ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferent nerves. From these results, our study might contributed to clarify the mechanism of overactive bladder and showed the way to neuro-stem cell transplantation therapy.Based on this study, we clinically applied the intravesical resiniferatoxin therapy for oberactive bladder because of spinal cord injuries. And we also showed the relationship between interstitial cystitis and neurokinin receptors. Less

今年，我们在开始神经干细胞移植之前专注于精确的膀胱过度活动症机制。特别是神经激肽受体和ATP。最近的研究提供了证据表明，尿道释放的ATP作用于骨盆传入神经的亚群在膀胱中的机械传入转导的主要作用。我们研究了通过全身性树脂毒素（RTX）预处理对辣椒素敏感的神经纤维的脱敏是否可以抵消膀胱内辣椒素、乙酸或ATP诱导的逼尿肌过度活动。或车辆。膀胱内滴注ATP（0.1或1.0 mM），辣椒素（30 μ M）或乙酸（pH 4.0）的效果进行了比较与膀胱内盐水。RTX，而不是其载体，显著增加阈值压力，排尿间隔，排尿量和膀胱c ...更多信息能力在溶剂预处理的大鼠中，膀胱内滴注辣椒碱或乙酸显著降低排尿间隔、排尿量和膀胱容量。然而，在RTX预处理的大鼠中，辣椒素和乙酸均不影响任何参数。另一方面，膀胱内ATP（0.1 mM）显着减少排尿间隔和排尿量在两组动物。在1.0 mM，ATP也增加了基础压力，降低了压力阈值排尿在这两个groups.The目前的结果支持的观点，增加细胞外ATP有一个作用，在大鼠膀胱的机械传入转导和ATP诱导的促进排尿反射介导的，至少部分，由辣椒素敏感的传入神经以外的神经。在此基础上，我们将树脂毒素膀胱灌注治疗脊髓损伤所致的膀胱过度活动症应用于临床。同时也揭示了间质性膀胱炎与神经激肽受体的关系。少