CBD-derived compound restores bladder function after spinal injury

Neurogenic lower urinary tract dysfunction (NLUTD) is a major secondary complication following spinal cord injury (SCI). CIAC001, a cannabidiol-derived small molecule, has been reported to exhibit anti-neuroinflammatory efficacy. This study aimed to investigate whether CIAC001 ameliorates SCI-induced bladder dysfunction by suppressing local neuroinflammation. Female C57BL/6 mice were subjected to severe compression SCI at the T9 level and randomized into Sham, SCI + Vehicle, and SCI + CIAC001 groups. The treatment group received daily intraperitoneal CIAC001 (8 mg/kg) for 28 days. Assessments included urography, measurement of renal function markers, bladder weight and histology (Masson's trichrome), voiding behavior analysis, cystometry, immunofluorescence staining for neuroinflammation markers (GFAP, C3, β3-Tubulin) in the spinal cord, and retrograde neural tracing from the bladder to the periaqueductal gray and pontine micturition center using pseudorabies virus. SCI led to significant bladder dilation, increased bladder weight, detrusor muscle thinning, voiding dysfunction (increased spot number), and impaired urodynamics (elevated non-voiding contractions, micturition pressure, and bladder capacity; reduced voiding efficiency). These changes were associated with marked neuroinflammation (astrogliosis, A1 phenotype induction) and reduced supraspinal neural connectivity. CIAC001 treatment significantly attenuated these pathological alterations: it reduced bladder weight and improved urodynamic parameters, suppressed spinal cord neuroinflammation (reduced C3+ A1 astrocytes, enhanced axonal regeneration), and promoted the re-establishment of bladder-related neural pathways. CIAC001 effectively ameliorates key symptoms of SCI-induced NLUTD in mice, primarily through suppressing neuroinflammation and facilitating neural repair. These findings highlight CIAC001 as a promising therapeutic candidate for neurogenic bladder dysfunction after SCI, warranting further mechanistic and translational investigation.