A ventral root avulsion injury model for neurogenic underactive bladder studies

Area of Science:

• Urology
• Neuroscience
• Regenerative Medicine

Background:

• Detrusor underactivity (DU) impairs bladder emptying, leading to incomplete and prolonged voiding.
• Diagnosing DU is complex, especially when co-occurring with other bladder conditions like detrusor overactivity or aging.
• The underlying pathobiology of DU and underactive bladder (UAB) remains poorly understood, hindering treatment development.

Purpose of the Study:

• To review neuropathic etiologies of DU, specifically traumatic injuries to the cauda equina (CE) and conus medullaris (CM).
• To highlight the need for clinically relevant animal models to study UAB and advance therapeutic strategies.
• To discuss the utility of lumbosacral ventral root avulsion (VRA) injury models in rats and non-human primates.

Main Methods:

• Review of existing literature on DU, CE/CM injuries, and animal models.
• Analysis of rat VRA injury models, comparing bilateral and unilateral lesions.
• Discussion of translational research, including large animal models (rhesus macaques) for UAB studies.

Main Results:

• Rat VRA models effectively mimic the clinical phenotype of CM/CE injuries.
• Bilateral VRA induces bladder areflexia, while unilateral VRA causes partial lower urinary tract and visceromotor reflex impairment.
• Surgical repair and pharmacological interventions show potential for augmenting micturition reflexes.

Conclusions:

• Traumatic CE/CM injuries represent a significant neuropathic cause of DU.
• VRA models provide valuable insights into DU pathobiology and potential treatments.
• Development of large animal models is crucial for advancing UAB research and clinical translation.