International Urology and Nephrology

, Volume 51, Issue 1, pp 41–52 | Cite as

Improved voiding function by deep brain stimulation in traumatic brain-injured animals with bladder dysfunctions

  • Chellappan Praveen Rajneesh
  • Chien-Hung Lai
  • Shih-Ching Chen
  • Tsung-Hsun Hsieh
  • Hung-Yen Chin
  • Chih-Wei PengEmail author
Urology - Original Paper



Traumatic brain injury (TBI) is a global scenario with high mortality and disability, which does not have an effectual and approved therapy till now. Bladder dysfunction is a major symptom after TBI, and this study deals with the alleviation of bladder function in TBI rats, with the aid of deep brain stimulations (DBS).


TBI was induced by weight drop model (WDM) and standardized with the experimental subjects with variable heights for weight dropping. The rats survived after TBI were considered for bladder dysfunction observations. DBS with variable stimulation parameters like cystometric analysis and MRI studies were also performed.


After experimental studies, TBI 2-m-height crash was determined as suitable parameter due to minimal mortality rate and significant reduction in the voiding efficiency from 67 to 28%, whereas DBS significantly reversed the value of voiding efficiency to 65–84%. MRI studies revealed the severity of TBI impact and DBS localization.


The results showed profound therapeutic effect of PnO-DBS on voiding functions and bladder control on TBI rats.


Deep brain stimulations PnO Traumatic brain injury Weight drop model Cystometric analysis 



The experimental procedures used in the present study were approved by the Institutional Animal Care and Use Committee (IACUC) of Taipei Medical University (TMU) and followed by the TMU IACUC guidelines to treat animals humanely and reduce animal suffering by use of appropriate anaesthesia and analgesics (IACUC Approval No. LAC-2013-0199).


This work was supported by the Taiwan Ministry of Science and Technology under the Grant Number MOST106-2221-E-038-010-MY3 and MOST107-2811-E-038-001 to C.W. Peng.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Ethical approval

This work was approved and conducted under the ethical guidance of Institutional Animal Care and Use Committee (IACUC) of Taipei Medical University (Approval No. LAC-2013-0199).

Research involving human and animal participants

This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    Finan DJ (2018) Biomechanical simulation of traumatic brain injury in the rat. Clin Biomech. Google Scholar
  2. 2.
    Corrigan DJ, Selassie WA, Orman AJ (2010) The epidemiology of traumatic brain injury. J Head Trauma Rehabil 25:72–80. Google Scholar
  3. 3.
    Moody JB, Liberman C, Zvara P, Smith PP, Freeman K, Zvarova K (2014) Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury (TBI) in rats. Neurourol Urodyn 33:1159–1164. Google Scholar
  4. 4.
    Jiang HH, Kokiko-Cochran NO, Li K, Balog B, Lin CY, Damaser SM, Lin V, Cheng JY, Lee YS (2013) Bladder dysfunction changes from underactive to overactive after experimental traumatic brain injury. Exp Neurol 240:57–63. Google Scholar
  5. 5.
    Miocinovic S, Lempka FS, Russo SG, Marks BC, Buston CR, Sakaie KE, Vitek JL, Mclntyre CC (2009) Experimental and theoretical characterization of the voltagedistribution generated by deep brain stimulation. Exp Neurol 216(1):166–176. Google Scholar
  6. 6.
    Jen E, Lin WC, Hsieh HT, Chiu YC, Lu TC, Chen SC, Chen MC, Peng CW (2007) Prototype deep brain stimulation system with closed-loop control feedback for modulating bladder functions in traumatic brain injured animals. J Med Biol Eng 38(3):337–349. Google Scholar
  7. 7.
    Kringelbach ML, Jenkinson N, Green AL, Owen SLF, Hansen PC, Cornelissen PL, Holliday IE, Stein J, Aziz TZ (2007) Deep brain stimulation for chronic pain investigated with magnetoencephalography. Neuro Rep 18(3):223–228Google Scholar
  8. 8.
    Anderson RJ, Frye MA, Abulseoud OA, Lee KH, McGillivray JA, Berk M, Tye SJ (2012) Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action. Neurosci Biobehav Rev 36:1920–1933. Google Scholar
  9. 9.
    Salanova V (2018) Deep brain stimulation for epilepsy. Epilepsy Behav. Google Scholar
  10. 10.
    Frederick C, Nucifora E, Woznica BJ, Lee N, Cascella A, Sawa (2018) Treatment resistant schizophrenia: clinical, biological, and therapeutic perspectives. Neuro Biol Dis. Google Scholar
  11. 11.
    Montgomery EB Jr, Baker KB (2000) Mechanisms of deep brain stimulation and future technical developments. Neurol Res 22(3):259–266. Google Scholar
  12. 12.
    Vitek JL (2002) Deep brain stimulation for Parkinson’s disease a critical re-evaluation of STN versus GPi DBS. Stereotact Funct Neurosurg 78:119–131. Google Scholar
  13. 13.
    Wallace BA, Ashkan K, Heise CE, Foote KD, Torres N, Mitrofanis J, Benabid AL (2007) Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys. Brain 130(8):2129–2145. Google Scholar
  14. 14.
    Veerakumar A, Berton O (2015) Cellular mechanisms of deep brain stimulation: activity-dependent focal circuit reprogramming? Curr Opin Behav Sci 1(4):48–55. Google Scholar
  15. 15.
    Schiff ND, Giacino JT, Kalmar K, Victor JD (2007) Behavioural improvements with Thalamic stimulation after severe traumatic brain injury. Nature 448:600–603. Google Scholar
  16. 16.
    Cernak L (2005) Animal models of head trauma. NeuroRX 2(3):410–422. Google Scholar
  17. 17.
    Marmarou A, Foda MAAE, van den Brink W, Campbell J, Kits H, Demetriadou K (2010) A new model of diffuse brain injury in rats part I: pathophysiology and biomechanics. J NeuroSurg 112(2):291–300Google Scholar
  18. 18.
    Foda MAAE, Marmarou A (1994) A new model of diffuse brain injury in rats: part II: morphological characterization. J Neurosurg 80(2):301–313Google Scholar
  19. 19.
    Noto H, Roppolo J, Steers W, De Groat W (1989) Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat. Brain Res 492(1):99–115. Google Scholar
  20. 20.
    Goddeyne C, Nichols J, Wu C, Anderson T (2015) Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats. J Neurophysiol 113:3268–3280. Google Scholar
  21. 21.
    Hsieh TH, Kang JW, Lai JH, Huang YZ, Rotenberg A, Chen YK, Wang JY, Chan SY, Chen SC, Chiang YH, Peng CW (2017) Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model. PLoS ONE 12(5):e0178186. Google Scholar
  22. 22.
    Chen QJ, Zhang CC, Lu H, Wang W (2014) Assessment of traumatic brain injury degree in animal model. Asian Pac J Trop Med 7(12):991–995. Google Scholar
  23. 23.
    Shohami E, Ginis I, Hallenbeck JM (1999) Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Fact Rev 10(2):119–130. Google Scholar
  24. 24.
    Denny-Brown DE, Russell RW (1941) Experimental concussion. Proc R Soc Med 34(11):691–692. Google Scholar
  25. 25.
    Lindgren S, Rinder L (1996) Experimental studies in head injury. Biophysik 3(2):174–180. Google Scholar
  26. 26.
    Ommaya KA, Grennarelli AT (1974) Cerebral concussion and traumatic unconsciousness correlation of experimental and clinical observations on blunt head injuries. Brain 97(1):633–654. Google Scholar
  27. 27.
    Sullivan GH, Martinez J, Becker PD, Miller JD, Griffith R, Wist AO (1976) Fluid-percussion model of mechanical brain injury in the cat. J Neurosurg 45:520–534Google Scholar
  28. 28.
    Nilsson B, Ponten U, Voigt G (1977) Experimental head injury in the rat Part 1: mechanics, pathophysiology, and morphology in an impact acceleration trauma mode. J Neurosurg 47:241–251Google Scholar
  29. 29.
    Dixon EC, Lyet GB, Povlishock TJ, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL (1989) A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119Google Scholar
  30. 30.
    Jang HJ, Kwon MJ, Cho KO (2018) Central regulation of micturition and its association with epilepsy. Int Neurourol J. Google Scholar
  31. 31.
    McMurray G, Casey HJ, Naylo MA (2006) Animal models in urological disease and sexual dysfunction. Brit J Pharmacol 147(S2):S62–S79. Google Scholar
  32. 32.
    Fry CH, Meng E, Young JS (2010) The physiological function of lower urinary tract smooth muscle. Auton Neurosci Basic Clin 154(1–2):3–13. Google Scholar
  33. 33.
    Andersson EK, Soler R, Füllhase C (2011) Rodent models for urodynamic investigation. Neurol Urodyn 30(5):636–646. Google Scholar
  34. 34.
    Oostra K, Everaert K, Laere V, M (1995) Urinary incontinence in brain injury. Brain Inj 10(6):459–464. Google Scholar
  35. 35.
    Khan Z, Hertanu J, Yang WC, Melman A, Leiter E (1981) Predictive correlation of urodynamic dysfunction and brain injury after cerebrovascular accident. J Urol 126(1):86–87. Google Scholar
  36. 36.
    Khan Z, Starer P, Yang WC, Bhola A (1990) Analysis of voiding disorders in patients with cerebrovascular accidents. Urology 35(3):265–270. Google Scholar
  37. 37.
    Wyndaele JJ, Meyer MJ, Sy AY, Claessens H (1986) Intracavernous injection of vasoactive drugs, an alternative for treating impotence in spinal cord injury patients. Paraplegia 24:271–275. Google Scholar
  38. 38.
    Blaivas GJ (1982) The neurophysiology of micturition: a clinical study of 550 patients. J Urol 127(5):958–963. Google Scholar
  39. 39.
    Kadow TB, Tyagi P, Chermansky JC (2015) Neurogenic causes of detrusor underactivity. Cur Blad Dysfunct Rep 10(4):325–331. Google Scholar
  40. 40.
    Kelly EC (2004) Evaluation of voiding dysfunction and measurement of bladder volume. Rev Urol 6(Suppl 1):S32–S37Google Scholar
  41. 41.
    Krasmik D, Krebs J, Ophoven VA, 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. Neurourol Urodyn 33:1202–1206. Google Scholar
  42. 42.
    Chew DJ, Zhu L, Delivopoulos E, Minev IR, Musick KM, Mosse CA, Craggs M, Donaldson N, Lacour SP, McMahon SB, Fawcett JW (2013) A microchannel neuroprosthesis for bladder control after spinal cord injury in rat. Sci Transl Med. Google Scholar
  43. 43.
    Benabid AL, Pollak P, Louveau A, Henry S, De Rougemont J (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for Bilateral Parkinson disease. Appl Neurophysiol 50:344–346. Google Scholar
  44. 44.
    Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P, Gay E, Payen I, Benazzouz A (1996) Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neuro Surg 84:203–214Google Scholar
  45. 45.
    Chen CS, Grill MW, Fan JW, Kou YR, Lin YS, Lai CH, Peng CW (2011) Bilateral pudendal afferent stimulation improves bladder emptying in rats with urinary retention. Br J Urol 109(7):1051–1058. Google Scholar
  46. 46.
    Klevmark B (2002) Volume threshold for micturition. Infuence of filling rate on sensory and motor bladder function. Scand J Urol Nephrol 210:6–10. Google Scholar
  47. 47.
    Kadow TB, Tyagi P, Chermansky JC (2015) Neurogenic causes of detrusor underactivity. Curr Blad Dysfunct Rep 10(4):325–331. Google Scholar
  48. 48.
    Seif C, Herzog J, Horst CV, Schrader B, Volkmann J, Deuschl G, Juenemann, Braun PM (2004) Effect of subthalamic deep brain stimulation on the function of the urinary bladder. Ann Neurol 55(1):118–120. Google Scholar
  49. 49.
    Jen E, Heish HT, Lu CT, Chen CM, Lee FJ, Lin TC, Chen SC, Chu PY, Peng CW, Lin CW (2016) Effects of pulsed radio frequency neuro modulations on the rat with over reactive bladder. Neurol Urodynamic 36(7):1734–1741. Google Scholar
  50. 50.
    Kruse NM, Noto H, Roppollo JR, Groat de W C (1990) Pontine control of the urinary bladder and external urethral sphincter in the rat. Brain Res 532(1–2):182–190. Google Scholar
  51. 51.
    Fan WJ, Li TY, Chen JJJ, Chen SC, Lin YS, Kou YR, Peng CW (2013) Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat. Am J Physiol Renal Physiol 305(9):F1332–F1134. Google Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.School of Biomedical Engineering, College of Biomedical EngineeringTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Physical Medicine and Rehabilitation, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Department of Physical Medicine and RehabilitationTaipei Medical University HospitalTaipeiTaiwan
  4. 4.Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of MedicineChang Gung UniversityTaoyuanTaiwan
  5. 5.Neuroscience Research CenterChang Gung Memorial HospitalLinkouTaiwan
  6. 6.Department of Obstetrics and GynaecologyTaipei Medical University HospitalTaipeiTaiwan
  7. 7.Department of Obstetrics and Gynecology, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  8. 8.Graduate Institute of Biomedical Optomechatronics, College of Biomedical EngineeringTaipei Medical UniversityTaipeiTaiwan

Personalised recommendations