TAC‐302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats

• Published in: Neurourology and urodynamics 2018-02, Vol.37 (2), p.681-689
• Main Authors: Yoshida, Shohei, Orimoto, Naoki, Tsukihara, Hiroshi, Noma, Takahisa, Hakozaki, Atsushi, Sasaki, Eiji
• Format: Article
• Language: English
• Subjects: bladder denervation; bladder outlet obstruction; cystometry; detrusor overactivity; TAC‐302
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.23375

Aims To evaluate the ability of TAC‐302, a cyclohexenoic fatty alcohol derivative, to enhance neurite outgrowth in cultured rat dorsal root ganglion (DRG) neurons, and the preventive effects of TAC‐302 on bladder denervation‐related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO). Methods Rat DRG neurons were cultured in the presence of TAC‐302. Cell numbers and neurite lengths were quantified after a 24 h culture. BOO was achieved by partial ligature of the proximal urethra in female rats. BOO rats were divided into three groups and orally treated with vehicle of 3 or 30 mg/kg TAC‐302 twice a day for 4 weeks. Cystometry was performed under conscious conditions. Immunohistochemical staining using anti‐PGP9.5 of the bladder muscle layer was performed, and the innervation area was scored. Results TAC‐302 significantly and dose‐dependently increased neurite outgrowth in cultured DRG neurons. BOO rats showed a decreased innervation area in the urinary bladder compared to sham‐operated rats. BOO‐induced denervation of the urinary bladder was partially prevented by oral treatment with TAC‐302. TAC‐302 significantly reduced the frequency of non‐voiding contraction (NVC) and residual urine volume (RUV) compared with the BOO vehicle group (P