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

Area of Science:

• Neuroscience
• Urology
• Immunology

Background:

• Traumatic brain injury (TBI) is linked to severe bladder dysfunction, including incontinence and lower urinary tract symptoms.
• The underlying mechanisms connecting brain degeneration and bladder control deficits remain poorly understood.
• Rostral brain regions are implicated in bladder function, but their specific role post-TBI is unclear.

Purpose of the Study:

• To investigate the link between TBI-induced brain degeneration and subsequent bladder dysfunction in a mouse model.
• To evaluate the efficacy of cis P-tau monoclonal antibody (cis mAb) in preventing TBI-related bladder dysfunction.
• To determine the specific brain regions affected by TBI that contribute to bladder control loss.

Main Methods:

• Repetitive moderate traumatic brain injury (rmdTBI) or sham injury was induced in male C57BL/6J mice.
• Mice received either cis P-tau monoclonal antibody (cis mAb) or control IgG.
• Void spot assays and urodynamic cystometry were used to assess bladder function; brain pathology was examined histologically.

Main Results:

• Age-dependent incontinence and overactive bladder were observed in control IgG mice 8 months post-injury, but not in cis mAb treated or sham mice.
• No significant bladder pathology was found in any group, suggesting central nervous system origins of dysfunction.
• Hyperphosphorylated tau deposition and neuroinflammation were present in the rostral (cortical and hippocampal) brain regions of control mice, but not in hindbrain regions controlling voiding reflexes.

Conclusions:

• Bladder dysfunction following TBI in this model results from damage to rostral brain regions, not the hindbrain.
• Rostral brain inputs are essential for maintaining normal bladder function.
• Targeting tau pathology with cis mAb offers a potential therapeutic strategy for TBI-induced bladder dysfunction.