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，导致脊髓损伤。对于脊髓损伤后的临床医生和患者来说，膀胱的管理是首要的。从历史上看，高膀胱压力和/或感染造成的肾脏损伤是此类损伤导致的常见死亡原因。感染仍然会增加死亡率和发病率，抗生素耐药性的风险加剧了这种情况。为了实现排尿--即30年前，伦敦MRC神经假体中心的GS Brindley开发了一种用于控制脊髓损伤(SCI)后膀胱的神经假体，这是一种完全自愿排尿(CVM)和替代昂贵的间歇无菌导尿术的昂贵过程。Brindley方法使用了骶前根刺激(SARS)，但就接受治疗的脊髓损伤人群比例而言，在欧洲并不流行，因为植入该装置的同时需要切断骶骨后(感觉神经)神经根(根切断术)，以防止膀胱充盈期间的反射性失禁和改善刺激排尿。显然，需要一种更能被广泛接受的新的神经假体(主要是因为不需要切断神经根)，此外，它还可以降低终生护理成本。这个项目的目的是设计和演示这样的装置。自引入以来，布林德利方法已经在几个方面进行了改进，试图解决上述问题。然而，尽管有这些进展，目前(A)没有令人满意的、实用的方法来检测慢性植入物中膀胱收缩的开始，以及(B)没有方法可以告知患者膀胱充盈程度以指示何时应该排空膀胱。这些都是设计完整假体的关键障碍，我们建议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(即对于刺激)。放置电极的合适部位是硬膜外根部；这在手术上很有吸引力，在布林德利手术中，电极通常植入在这里。为了使神经与人类的神经相似，有必要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.