Effects of Central Neuromodulation with Functional Electrical Stimulation on Bladder Functions in Traumatic Brain Injured Rats

Traumatic brain injury (TBI) is a common accident, which usually results from motor vehicle or falling events. TBI usually caused serious brain tissue damage, and its mortality rate is quite high. With advances in medical technology, the survival rate of TBI has improved greatly. However, most patients have a permanent brain defect, which cause motor, sensory, cognitive, behavioral, language, and urinary system dysfunctions for life. The etiology of urinary system dysfunction may attribute to the damage of the pathways between the central micturition center and the central nervous system (CNS), and thus the central micturition center could not operate normally. The chronic voiding dysfunction will likely induce lower urinary tract infections, urinary reflux and urinary incontinence, and even lead to renal failure or death. Therefore, the voiding dysfunction is an important issue among all TBI patients. For clinical treatment, there is still lack of an efficient approach to handle the physical dysfunction caused by the CNS lesion, and thus deep brain stimulation (DBS) may be a new alternative treatment direction. Currently, the development of DBS has been used to treat the movement dysfunction of Parkinson's patients. In addition, recently FDA has conditionally approved the therapeutic usage of DBS in epilepsy patients. Other applications of DBS in the CNS diseases, such as chronic pain, depression, autism, and voiding dysfunctions, are also developing in many international research centers. The purpose of this study is to develop a set of DBS scheme via neural engineering methods, and the scheme would be applied in the treatment of voiding dysfunctions caused by TBI. A TBI animal model with voiding dysfunction will be utilized in this project. Under this animal model, the stimulation electrode will be implanted in specific areas of deep brain, and a series of neural engineering and electrophysiological experiments will be conducted. In this three-year experiment, the aim of the first-year study is to investigate the regulatory mechanism and pathway between brain and lower urinary tract (LUT) in rats after TBI intervention. In the second year, on the basis of the experimental results in the first year, we further investigate the therapeutic effects of different electrical stimulation parameters on the bladder function in rats under anesthetic conditions (acute animal experiments). Optimal stimulation parameters and schemes will be established and those results will be the guideline for the last-year experiments. In the third year, an implantable electrode and a pressure sensor will be long-term implanted in the brain and bladder in TBI rats (chronic animal studies). According to the optimal brain stimulation parameters established in the second year, we will further verify the therapeutic effects of brain electrical stimulation on bladder function in awake TBI rats. It is expected that a sophisticated DBS scheme will be established within 3 years. Since the DBS hardware technology is now mature for the treatment of Parkinson's disease, our developed DBS scheme may have the possibility to quickly enter clinical trial phase by means of cooperation with DBS manufactures (combing with their hardware technique). In this way, it does not only shorten the schedule of this technology applied in clinic, and is also to improve its clinical value and success rate.