Detecting bladder volume and pressure from sacral nerve signals: the key to future artificial control

这个项目是关于治疗尿失禁，脊髓损伤的后果。膀胱的管理是最重要的临床医生和病人的创伤后脊髓。从历史上看，由于高膀胱压力和/或感染引起的肾损伤是这种损伤导致死亡的常见原因。感染仍然会增加死亡率和发病率，而抗生素耐药性的风险又使情况更加恶化。为了实现排尿，即完全自主排尿（CVM），并作为间歇性无菌导尿的昂贵过程的替代方案，30年前，伦敦MRC神经假体部门的GS Brindley开发了一种用于控制脊髓损伤（SCI）后膀胱的神经假体。Brindley方法采用骶神经前根刺激（SARS），但在欧洲并不流行，就治疗的SCI人群的比例而言，因为植入该装置伴随着切割骶后（感觉）神经根（神经根切断术），以防止膀胱充盈期间的反射性尿失禁并改善刺激排尿。显然，需要一种新的神经假体，它可以被更广泛地接受（主要是因为不需要神经根切断术），此外，它还可以减少护理的终身成本。本项目的目的是设计和演示这样的设备。自引入以来，布林德利方法已在多个方面进行了改进，试图解决上述问题。然而，尽管有这些发展，目前（a）不存在令人满意的实用方法来检测慢性植入物中膀胱收缩的开始，以及（B）没有方法可用于通知患者膀胱充满程度以指示何时应该排空膀胱。这些是设计完整假体的关键障碍，我们提出的解决方案是使用膀胱神经信号本身，因为手术植入的电极无论如何都是必不可少的（即用于刺激）。硬膜外神经根是电极的合适位置;这在手术上是有吸引力的，在Brindley手术中，电极通常植入此处。为了使神经类似于人类的神经，必须使用大型实验动物作为临床前模型，我们建议使用绵羊进行这些实验。

This project is about the treatment of urinary incontinence, consequent of damage to the spinal cord. Managing the urinary bladder is of the first importance to clinicians and patients following trauma to the spinal cord. Historically, kidney damage due to high bladder pressures and/or infection was the usual cause of death resulting from such an injury. Infections still raise mortality and morbidity, exacerbated by the risk of antibiotic resistance. In order to achieve urination-i.e. complete voluntary micturition (CVM) and as an alternative to the expensive process of intermittent sterile catheterisation, a neuroprosthesis for controlling the bladder after spinal cord injury (SCI) was developed by GS Brindley at the MRC Neurological Prostheses Unit in London 30 years ago. The Brindley method employs sacral anterior root stimulation (SARS) but is not popular in Europe, in terms of the fraction of the SCI population treated, because implantation of the device is accompanied by cutting the sacral posterior (sensory) nerve roots (rhizotomy) to prevent reflex incontinence during bladder filling and improve stimulated voiding. Clearly there is a need for a new neuroprosthesis that is more widely acceptable (primarily because no rhizotomy is necessary) and which, in addition, reduces the lifetime cost of care. The aim of this project is to design and demonstrate such a device. Since its introduction, the Brindley method has been improved in several ways in attempts to address the problems mentioned. However, in spite of these developments, at present (a) no satisfactory, practical method exists for detecting the onset of bladder contractions in a chronic implant and, (b) no method is available to inform the patient of the level of bladder fullness to indicate when the bladder should be emptied. These are critical obstacles to the design of a complete prosthesis and our proposed solution is to use the bladder neural signals themselves since surgically implanted electrodes are essential anyway (i.e. for stimulation). A suitable site for the electrodes is the extradural roots; this is surgically attractive and electrodes are routinely implanted here in the Brindley procedure. In order that the nerves are similar to those in man, it is essential to use a large experimental animal as a preclinical model and we propose to use sheep for these experiments.