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. 2010 Sep;184(3):1204-10.
doi: 10.1016/j.juro.2010.04.066. Epub 2010 Jul 21.

Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats

Minoru Miyazato  1 , Kimio Sugaya, Seiichi Saito, Michael B Chancellor, William F Goins, James R Goss, William C de Groat, Joseph C Glorioso, Naoki Yoshimura
Affiliations

Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats

Minoru Miyazato et al. J Urol. 2010 Sep.

Abstract

Purpose: We investigated whether replication defective herpes simplex virus vectors encoding genes of glutamic acid decarboxylase, the gamma-aminobutyric acid synthesis enzyme, could suppress detrusor-sphincter dyssynergia in rats with spinal cord injury.

Materials and methods: One week after spinalization herpes simplex virus vectors expressing glutamic acid decarboxylase and green fluorescent protein were injected into the bladder wall. Spinal cord injured rats without herpes simplex virus injection (sham treated) and those injected with LacZ encoding herpes simplex virus vectors served as controls. Three weeks after viral injection we simultaneously recorded urethral and intravesical pressure in awake rats.

Results: In the glutamic acid decarboxylase group the urethral pressure increase during bladder contraction was significantly decreased by 77% to 79% compared with that in the sham treated and LacZ groups. Bladder activity and urethral baseline pressure did not differ among the 3 groups. Intrathecal application of the gamma-aminobutyric acid-A receptor antagonist bicuculline almost completely reversed the decrease in the urethral pressure increase during bladder contractions while intrathecal saclofen (Tocris Cookson, Ellisville, Missouri), a gamma-aminobutyric acid-B receptor antagonist, partially reversed it. In the glutamic acid decarboxylase group the mRNA of glutamic acid decarboxylase 67 was significantly increased in L6-S1 dorsal root ganglia, which is where bladder afferents originate, compared with that in the LacZ group.

Conclusions: Herpes simplex virus based glutamic acid decarboxylase gene transfer to bladder afferent pathway may represent a novel approach to detrusor-sphincter dyssynergia in cases of spinal cord injury.

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Figures

Fig. 1
Fig. 1
Simultaneous recordings of intravesical pressure and urethral pressure in SCI rats with HSV-LacZ (A) or HSV-GAD treatment (B). A: DSD evidenced by urethral pressure rises during bladder contractions was shown. B: However, after the HSV-GAD treatment, increases in urethral pressure during bladder contractions were reduced.
Fig. 2
Fig. 2
Simultaneous recordings of intravesical pressure and urethral pressure in a HSV-GAD treated SCI rat before (A) and after 0.1 μg of intrathecal application of bicuculline (B). A: Small-amplitude increases of urethral pressure during bladder contractions were shown. B: After intrathecal bicuculline (0.1 μg), amplitudes of intravesical pressure and urethral pressure were increased.
Fig. 3
Fig. 3
Simultaneous recordings of intravesical pressure and urethral pressure in a HSV-GAD treated SCI rat before (A) and after 1 μg of intrathecal application of saclofen (B). A: A synergic pattern as evidenced by a negative shift of urethral pressure during bladder contractions was shown. B: After intrathecal 1 μg of saclofen, intravesical pressure did not change, but urethral pressure amplitude was increased.
Fig. 4
Fig. 4
(A) GAD67 mRNA/β-actin mRNA ratio in L6-S1 DRG in HSV-LacZ and HSV-GAD-treated SCI rats. GAD67 mRNA/β-actin mRNA ratio in L6-S1 DRG was significantly increased in HSV-GAD-treated SCI rats compared with HSV-LacZ-treated SCI rats. Values are the mean ± SE. ** p<0.01 when compared between HSV-LacZ and HSV-GAD-treated SCI rats.
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References

    1. Holstege G, Griffiths D, de Wall H, et al. Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J Comp Neurol. 1986;250:449. - PubMed
    1. de Groat WC, Yoshimura N. Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. Prog Brain Res. 2006;152:59. - PubMed
    1. Miyazato M, Sugaya K, Nishijima S, et al. Intrathecal or dietary glycine inhibits bladder and urethral activity in rats with spinal cord injury. J Urol. 2005;174:2397. - PubMed
    1. Nishizawa O, Igawa Y, Satoh T, et al. Effects of glutamate receptor antagonists on lower urinary tract function in conscious unanesthetized rats. Adv Exp Med Biol. 1999;462:275. - PubMed
    1. Yokoyama O, Mita E, Akino H, et al. Roles of opiate in lower urinary tract dysfunction associated with spinal cord injury in rats. J Urol. 2004;171:963. - PubMed

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