Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats

Satoshi Seki, Katsumi Sasaki, Matthew O. Fraser, Yasuhiko Igawa, Osamu Nishizawa, Michael B. Chancellor, William C. De Groat, Naoki Yoshimura

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Purpose: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. Materials and Methods: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 μg. daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. Results: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30% to 35%) and L6 spinal cord (53%) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. Conclusions: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.

Original languageEnglish
Pages (from-to)2269-2274
Number of pages6
JournalJournal of Urology
Volume168
Issue number5
Publication statusPublished - Nov 1 2002
Externally publishedYes

Fingerprint

Abnormal Reflexes
Nerve Growth Factor
Spinal Cord
Urinary Bladder
Spinal Ganglia
Antibodies
Pressure
Spinal Cord Injuries
Catheters
Afferent Pathways
Afferent Neurons
Spinal Nerve Roots

Keywords

  • Bladder
  • Ganglia, spinal
  • Nerve growth factor
  • Rats, Sprague-Dawley
  • Spinal cord injuries

ASJC Scopus subject areas

  • Urology

Cite this

Seki, S., Sasaki, K., Fraser, M. O., Igawa, Y., Nishizawa, O., Chancellor, M. B., ... Yoshimura, N. (2002). Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. Journal of Urology, 168(5), 2269-2274.

Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. / Seki, Satoshi; Sasaki, Katsumi; Fraser, Matthew O.; Igawa, Yasuhiko; Nishizawa, Osamu; Chancellor, Michael B.; De Groat, William C.; Yoshimura, Naoki.

In: Journal of Urology, Vol. 168, No. 5, 01.11.2002, p. 2269-2274.

Research output: Contribution to journalArticle

Seki, S, Sasaki, K, Fraser, MO, Igawa, Y, Nishizawa, O, Chancellor, MB, De Groat, WC & Yoshimura, N 2002, 'Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats', Journal of Urology, vol. 168, no. 5, pp. 2269-2274.
Seki S, Sasaki K, Fraser MO, Igawa Y, Nishizawa O, Chancellor MB et al. Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. Journal of Urology. 2002 Nov 1;168(5):2269-2274.
Seki, Satoshi ; Sasaki, Katsumi ; Fraser, Matthew O. ; Igawa, Yasuhiko ; Nishizawa, Osamu ; Chancellor, Michael B. ; De Groat, William C. ; Yoshimura, Naoki. / Immunoneutralization of nerve growth factor in the lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. In: Journal of Urology. 2002 ; Vol. 168, No. 5. pp. 2269-2274.
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abstract = "Purpose: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. Materials and Methods: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 μg. daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. Results: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30{\%} to 35{\%}) and L6 spinal cord (53{\%}) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. Conclusions: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.",
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AU - Seki, Satoshi

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AU - Fraser, Matthew O.

AU - Igawa, Yasuhiko

AU - Nishizawa, Osamu

AU - Chancellor, Michael B.

AU - De Groat, William C.

AU - Yoshimura, Naoki

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N2 - Purpose: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. Materials and Methods: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 μg. daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. Results: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30% to 35%) and L6 spinal cord (53%) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. Conclusions: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.

AB - Purpose: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. Materials and Methods: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 μg. daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. Results: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30% to 35%) and L6 spinal cord (53%) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. Conclusions: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.

KW - Bladder

KW - Ganglia, spinal

KW - Nerve growth factor

KW - Rats, Sprague-Dawley

KW - Spinal cord injuries

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