The structural effect of systemic NGF treatment on permanently axotomised dorsal root ganglion cells in adult rats.
The effect of systemic NGF treatment on loss and shrinkage of dorsal root ganglion cells was studied in adult male rats after permanent axotomy. Nineteen 16 to 18-wk-old rats had their right 5th lumbar spinal nerve ligated and cut approximately 7 mm peripheral to the ganglion. Two days before the operation, treatment with subcutaneous injections of human recombinant NGF (1.0-0.5 mg/kg/day) was started in 9 test rats; 10 controls were given saline injections. After 1 mo the levels of substance P (SP) and calcitonin gene related peptide (CGRP) were significantly increased in intact sciatic nerve. The number and mean volume of perikarya were estimated using assumption-free stereological techniques including vertical sections, the Cavalieri principle, optical disectors, the planar rotator and systematic sampling techniques. Systemic NGF administration had no influence on survival of primary sensory neurons after axotomy. The number of perikarya was 14300 (S.D. = 1800) in axotomised ganglia in control rats versus 14700 (S.D. = 2100) in axotomised ganglia of NGF treated rats. The reduction of perikarya volume after axotomy was significantly less after NGF treatment (11600 microm3 in the control group versus 8000 microm3 in the NGF treated group). However, the apparent protection of NGF-treatment on perikaryal volume is explained by a hitherto unrecognised size effect on nonaxotomised dorsal root ganglion cells. The untreated rats had a mean volume of 24700 microm3 (S.D. = 2700 microm3) whereas rats treated with NGF had a volume of 20400 microm3 (S.D. = 1700 microm3) on the nonaxotomised side. In conclusion, systemic NGF treatment in adult rats has no effect on dorsal root ganglion cell loss in permanent axotomy whereas perikaryal size of intact nonaxotomised cells is reduced.
Tandrup
T
T
Department of Neurology, University Hospital of Aarhus, Denmark. trine@akh phd.au.dk
Vestergaard
S
S
Tomlinson
D R
DR
Diemel
L T
LT
Jakobsen
J
J
D000818:Animals; D019771:Axotomy; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012584:Sciatic Nerve / Q000737:chemistry; D013127:Spinal Nerves / Q000601:surgery; D013373:Substance P / Q000032:analysis; D017211:Treatment Failure
D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide