Prototype Deep Brain Stimulation System with Closed-Loop Control Feedback for Modulating Bladder Functions in Traumatic Brain Injured Animals
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Traumatic brain injury (TBI) typically causes permanent brain tissue damage, which leads to permanent severe voiding dysfunction. Urinary retention is often refractory to standard therapies, and most patients require self-catheterization, which results in frequent urinary tract infections and reduces quality of life. Deep brain stimulation (DBS) might be a feasible alternative approach for treating bladder disorders in patients with TBI. In this study, we developed a DBS system with a closed-loop control strategy and determined the feasibility of this DBS system for improving bladder voiding function in a TBI animal model. A prototype of the DBS system was designed, fabricated and integrated with a closed-loop control algorithm based on the real-time external urethral sphincter-electromyogram feedback. A series of animal experiments was conducted to determine whether the feedback algorithm accurately detects the bladder status during cystometric measurements. Subsequent animal experiments were conducted to implement this DBS system and determine the performance of the closed-loop strategy for improving bladder functions in the TBI animal model. We successfully implemented a closed-loop algorithm for DBS control, and the accuracy of the bladder voiding phase detection was > 90%. Our system significantly improved the voiding efficiency in TBI rats from 22 to 74%. Although the prototype of the DBS feedback system was fabricated with surface-mounted device components and mounted on a 3D printed circuit board, the design principles and animal experience gathered from this research can serve as a basis for developing a new implantable bladder controller in the future.
KeywordsTraumatic brain injury Urinary retention Deep brain stimulation Electromyogram Closed-loop
This study was supported by grants from the Ministry of Science and Technology (MOST106-2221-E-038-010-MY3, MOST103-2221-E-038-007-MY3, and NSC 102-2320-B-002-040 -MY2) and by the R&D Foundation of Urological Medicine, Taiwan. The authors also thank Professors Te-Son Kuo and Shuenn-Tsong Young for their outstanding technical support.
- 1.Faul, M., Xu, L., Wald, M. M., & Coronado, V. (2010). Traumatic brain injury in the United States. Atlanta, GA: National Center for injury Prevention and Control, Centers for disease Control and Prevention.Google Scholar
- 7.Moiyadi, A. V., Devi, B. I., & Nair, K. (2007). Urinary disturbances following traumatic brain injury: Clinical and urodynamic evaluation. NeuroRehabilitation, 22(2), 93–98.Google Scholar
- 24.Krasmik, D., Krebs, J., van Ophoven, A., & Pannek, J. (2014). Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury. Neurourology and Urodynamics, 33(8), 1202–1206.CrossRefGoogle Scholar
- 30.Blok, B. F., De Weerd, H., & Holstege, G. (1995). Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition center or M-region in the cat: A new concept for the organization of the micturition reflex with the periaqueductal gray as central relay. Journal of Comparative Neurology, 359(2), 300–309.CrossRefGoogle Scholar
- 39.Ekmark-Lewén, S., Flygt, J., Kiwanuka, O., Meyerson, B. J., Lewén, A., Hillered, L., et al. (2013). Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes. Journal of Neuroinflammation, 10(1), 44.CrossRefGoogle Scholar