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

在这一年里，在开始神经干细胞移植之前，我们重点研究了膀胱过度活跃的确切机制。特别是，我们重点研究了神经激肽受体和三磷酸腺苷。最近的研究已经提供了证据表明，尿路释放的ATP作用于盆腔传入神经的亚群，在膀胱的机械传入转导中起着重要作用。为探讨全身树脂素(RTX)对辣椒素敏感神经纤维的脱敏作用是否能对抗由辣椒素、冰醋酸或ATP引起的逼尿肌过度活动，SD雌性大鼠分别于注射RTX(0.3 mg/kg)前和注射RTX后24 h进行了膀胱测量。或者是车辆。比较三磷酸腺苷(0.1或1.0 mM)、辣椒素(30微米)或冰醋酸(pH 4.0)膀胱内灌注的效果。RTX，但不是它的载体，显著增加了阈值压力、排尿间隔、尿量和膀胱c-…。更有能力。在赋形剂处理的大鼠中，膀胱内注入辣椒素或醋酸显著减少了排尿间隔、尿量和膀胱容量。然而，在RTX预处理的大鼠中，辣椒素和醋酸都不影响任何参数。另一方面，膀胱内注入0.1 mM的三磷酸腺苷显著减少了两组动物的排尿间隔和尿量。在1.0 mM时，ATP还使两组大鼠的基础压升高，排尿压力阈值降低。本研究结果支持细胞外增加的ATP在大鼠膀胱力学传入传导中的作用，并且ATP诱导的排尿反射的易化至少部分是由神经而不是辣椒素敏感的传入神经介导的。本研究结果有助于阐明膀胱过度活动症的发病机制，为神经干细胞移植治疗提供新的思路。在此基础上，我们临床应用白藜芦醇膀胱内注射疗法治疗脊髓损伤引起的膀胱过度活动症。我们还显示了间质性膀胱炎与神经激肽受体的关系。较少

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