Application of Functional Electrical Stimulation on the Study of Nerve Regeneration in the Rat with Diabetic Neuropathy

In Taiwan, diabetes mellitus (DM) is a high prevalent disorder among people, which strictly threatens to everyone’s healthy condition. Severe DM can induce neuropathy and cause many complicated complications, such as retinal pathology, cardiovascular disease, chronic renal failure, and cystopathy etc. The diabetic cystopathy is associated with the impairment of the nerve system in lower urinary tract (LUT). Its pathological mechanism might be due to the chronic accumulation of lots of sorbitol and fructose on nerve tissue, therefore, which causes irreversible damage on nerve system. However, the detailed mechanisms of cystopathy remain unclear. For example, what kinds of alterations happened on LUT system when autonomic nerves destroyed by DM? Did the undamaged nerve fibers produce compensation effects on LUT for the sake of keeping normal bladder functions while most of nerve fibers damaged? Did the body actively repair the damaged nerve fibers in order to maintain the normal voiding function when these fibers under unbalanced condition of carbohydrate metabolism? Regarding peripheral nerve regeneration, several studies demonstrated electrical current stimulation (ECS) could accelerate axon regeneration or enhance damaged nerve repair in in-vivo animal models. However, people who suffered from irreversible nerve damage were usually elderly and with chronic diseases. Therefore, the physiological microenvironment affected the ability of nerve repair and regeneration should be seriously considered. In this study, we will choose diabetic rats as our animal model to investigate the neuropathic mechanisms and the possibility of nerve regeneration in LUT via neural engineering technique. A biocompatible micro-implantable stimulator system will be implanted in animals to conduct the pelvic nerve stimulation for 12 weeks. The entire study will be divided into three years. In first year the basically pathological mechanism of neuromuscular disorder in LUT system will be investigated. On the basis of the first-year’s results, the second-year experiment will further evaluate the micro-effect of ECS on nerve regeneration. In the final year, we will assess the entire functional changes of LUT system during the process of ECS. The changes between physiological microenvironment and bladder functions will also be determined. It is expected that the pathological changes and the effects of ECS on the treatment of the damaged nerve will be established within three years. If the results demonstrated that the ECS approach can reduce nerve damage, improve blood supply, and guide axon regeneration, ECS will be practically used and combined with the control of blood sugar and drug administration in clinical treatment. It is believed that the DM patients will get more sophisticated treatment, and various diabetic organ dysfunctions can be effectively cured in the future.