Traumatic Brain Injury-related voiding dysfunction in mice is caused by damage to rostral pathways, altering inputs to the reflex pathways

Sci Rep. 2019 Jun 14;9(1):8646. doi: 10.1038/s41598-019-45234-8.


Brain degeneration, including that caused by traumatic brain injury (TBI) often leads to severe bladder dysfunction, including incontinence and lower urinary tract symptoms; with the causes remaining unknown. Male C57BL/6J mice underwent repetitive moderate brain injury (rmdTBI) or sham injury, then mice received either cis P-tau monoclonal antibody (cis mAb), which prevents brain degeneration in TBI mice, or control (IgG). Void spot assays revealed age-dependent incontinence in IgG controls 8 months after injury, while cis mAb treated or sham mice showed no dysfunction. No obvious bladder pathology occurred in any group. Urodynamic cystometry in conscious mice revealed overactive bladder, reduced maximal voiding pressures and incontinence in IgG control, but not sham or cis mAb treated mice. Hyperphosphorylated tau deposition and neural tangle-like pathology occurred in cortical and hippocampal regions only of IgG control mice accompanied with post-traumatic neuroinflammation and was not seen in midbrain and hindbrain regions associated with bladder filling and voiding reflex arcs. In this model of brain degeneration bladder dysfunction results from rostral, and not hindbrain damage, indicating that rostral brain inputs are required for normal bladder functioning. Detailed analysis of the functioning of neural circuits controlling bladder function in TBI should lead to insights into how brain degeneration leads to bladder dysfunction, as well as novel strategies to treat these disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain Injuries, Traumatic / physiopathology*
  • Male
  • Mice, Inbred C57BL
  • Phenotype
  • Reflex / physiology*
  • Temperature
  • Urinary Bladder / pathology
  • Urinary Bladder / physiopathology
  • Urinary Bladder, Overactive / physiopathology
  • Urination / physiology*
  • tau Proteins / metabolism*


  • tau Proteins