Can Herpes Simplex Virus Vector-Mediated Gene Transfer of Kynurenine Aminotransferase Reduce Urethral Resistance in Spinal Cord Injured Rats?

Aim: To explore if replication-defective herpes simplex virus (HSVrd) vector-mediated gene transfer of kynurenine aminotransferase (KAT) can reduce urethral resistance in spinal cord injured rats. Methods: The HSVrd-KAT II vector was constructed, Sprague-Dawley rats was spinalized with complete transection of the T10 spinal cord. Viral suspension of HSVrd or HSVrd-KAT II (1×107 plaque-forming units) was injected into 4 sites around the bladder base, cystometry was recorded. The KAT II positive neurons, ratio of KAT II/GADPH proteins and KAT II/β-actin mRNA in L6-S1 dorsal root ganglia (DRG) were examined. Results: The number and amplitude of non-voiding bladder contraction (NVC), Detrusor Leak Point Pressur (DLPP) and Maximum Cystometric Capacity (MCC) were decreased significantly by 59.6-61.1%, 21.6-24.2%, 30.3- 34.4% and 44.1-46.5% (P<0.01), and the Bladder Emptying Efficiency (BEE) and the time to first NVC were increased significantly by 40.7-47.7% and 30.1- 49.0% (P<0.01), respectively, in the HSVrd-KAT II group compared to sham or HSVrd group. The vectors are transported to L6-S1 dorsal root ganglia and up-regulate the expression of KAT II. Conclusion: The HSVrd-KAT II vectors injected into the bladder wall can reduce the urethral resistance, improved DSD and BEE in SCI rats, possibly due to suppressing C-fiber bladder afferents and N-Methyl-D-Aspartate Receptors (NMDAR) blockade in the DRG and spinal cord.