Interactions between Urological and Locomotor Systems during Treadmill Training i

描述（由申请人提供）：脊髓损伤（SCI）会对上、下尿路产生不利影响。目前还没有有效的治疗泌尿功能障碍的方法。控制排尿功能对这类患者至关重要，因为这会影响患者的独立性、整体健康和自我形象。目前使用各种药物和手术治疗的尝试都有意想不到的副作用，而且效果有限。我们的目标之一是提供一种天然的治疗选择。体重支持的跑步机训练正在推进我们对脊髓如何学习和适应的认识，其对脊髓损伤患者的积极影响也在不断增加。我们从患者的临床观察中发现，步进训练对膀胱维护有有益的结果，并且四肢和膀胱之间存在抑制相互作用。因此，我们建议在临床相关的动物模型中研究这些观察结果，以确定所涉及的机制。86只雄性大鼠使用IH撞击或装置在T8脊柱水平受到225 kdyn的挫伤。在26只大鼠的比目鱼肌和胫前肌中植入膀胱导管和肌电图线，以确定有害和无害的膀胱传入输入对完整、脊髓损伤和炎症条件下运动（膀胱-躯体）表现的影响。c -纤维输入的作用也将通过辣椒素预处理来确定。膀胱炎症和肿胀可能改变腰骶神经的感觉输入，进而改变运动输出和脊柱学习的能力。从受伤后14天开始，20只大鼠每天在跑步机上进行8周的手动辅助训练。另外两组前肢训练组（n=20）和未训练组（n=20）同时进行测试。功能泌尿学数据将通过1)有意识的膀胱测量-导管注入生理盐水和2)利用代谢监测系统收集自然排尿模式来获得。脊髓损伤后11周的晚期分子研究将评估运动对膀胱中各种神经营养因子mRNA含量的调节，这些神经营养因子在运动和膀胱功能障碍文献中都被认为是重要的调节剂。因此，本研究将首次探讨运动疗法对包括逼尿肌、外尿道括约肌和肢体肌肉在内的脏器和躯体结构之间的脊髓介导反射关系的影响。尽管这些反射在正常受试者中部分被掩盖，但在上运动神经元疾病或脊髓损伤后，这些反射非常明显。本研究的每个部分都是专门为适用于脊髓损伤患者和运动训练等活动疗法而设计的。

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in detrimental effects on the upper and lower urinary tract. Currently there is no effective therapy for urological dysfunction. Having control over voiding function is of primary importance to this patient population as this affects independence, overall health, and self-image. Current attempts at treatments with various drugs and surgeries have unwanted side effects and limited success. One of our goals is to provide a natural therapeutic alternative. Body weight supported treadmill training is advancing our knowledge on how the spinal cord can learn and adapt, and the results of its positive effects for SCI patients continues to grow. We have clinical observations from patients that step training can have beneficial outcomes on bladder maintenance and that there is an inhibitory interaction between the limbs and the bladder. Therefore, we propose to study these observations in a clinically relevant animal model to identify mechanisms involved. Eighty-six male rats will receive a 225 kdyn force contusion injury at the T8 spinal level using the IH impact or device. Twenty-six rats will be implanted with a bladder catheter and EMG wires in the soleus and tibialis anterior muscles to determine the influence of noxious and innocuous bladder afferent input on locomotor (vesico-somatic) performance in intact, SCI, and inflammatory conditions. The role of C-fiber inputs will also be determined via capsaicin pre-treatment. Inflammation and distention from bladder may be altering sensory inputs for the lumbosacral cord, in turn altering the ability for locomotor output and spinal learning. Beginning 14 days post-injury, twenty rats will undergo daily step training on a treadmill with manual assistance for 8 weeks. Two other groups forelimb trained (n=20) and non-trained (n=20) will be tested simultaneously. Functional urological data will be obtained with 1) conscious cystometry- catheter infused saline and 2) natural voiding patterns gathered using a metabolic monitoring system. Terminal molecular studies eleven weeks post- SCI will assess the exercise's regulation of bladder mRNA content of various neurotrophic factors, which have been identified as important modulators in both the exercise and bladder dysfunction literature. Thus, this study will be the first to investigate the influence of exercise therapy on the spinally mediated reflexive relationship between viscera and somatic structures involving detrusor, external urethral sphincter, and limb musculature. Although partially masked in normal subjects, these reflexes are highly apparent after an upper motor neuron disease or SCI. Each part of this study is specifically designed to be applicable to the SCI patient and activity based therapies such as locomotor training. PUBLIC HEALTH RELEVANCE: Both quadriplegics and paraplegics rank bladder function as one of the most important factors affecting their quality of life, and 96.5% of 681 survey respondents believe that exercise is an important part of functional recovery yet at least 63.6% do not have access to a trained therapist to oversee their regiments. With over 1 million people in the U.S. alone affected by SCI and the annual cost in federal funds estimated at $9.7 billion, the knowledge gained from our study on locomotor training effects on bladder function will not only be immediately applicable to patients, providing immense improvements in quality of life, but also reduce life-long burdens on patient, family, and care centers.