Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder.
OBJECTIVE
To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)-mediated neurogenic bladder in rats.


METHODS
In all, 40 female Sprague-Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 microg/rat), VEGF (2 microg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (alpha-actin), Masson's trichrome and protein gene product 9.5, respectively.


RESULTS
Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups.


CONCLUSIONS
This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.
Kikuno
Nobuyuki
N
Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, CA, USA.
Kawamoto
Ken
K
Hirata
Hiroshi
H
Vejdani
Kaveh
K
Kawakami
Kazumori
K
Fandel
Thomas
T
Nunes
Lora
L
Urakami
Shinji
S
Shiina
Hiroaki
H
Igawa
Mikio
M
Tanagho
Emil
E
Dahiya
Rajvir
R
D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects / Q000637:transplantation; D005260:Female; D006085:Graft Survival; D020932:Nerve Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012038:Regeneration / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications*; D023822:Tissue Engineering; D001743:Urinary Bladder / Q000502:physiology*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor