title: Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugaya
authors.forename: Seiichi
authors.initials: S
authors.lastname: Saito
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: William F
authors.initials: WF
authors.lastname: Goins
authors.forename: James R
authors.initials: JR
authors.lastname: Goss
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D005968:Glutamate Decarboxylase / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus; D013119:Spinal Cord Injuries / Q000150:complications*; D001750:Urinary Bladder, Neurogenic / Q000209:etiology* / Q000628:therapy*
chemical_list: D005968:Glutamate Decarboxylase