Recombinant human glial growth factor 2 (rhGGF2) improves functional recovery of crushed peripheral nerve (a double-blind study).
This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.
Chen
L E
LE
Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Liu
K
K
Seaber
A V
AV
Katragadda
S
S
Kirk
C
C
Urbaniak
J R
JR
D000818:Animals; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D020904:Glia Maturation Factor; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D020904:Glia Maturation Factor; D006131:Growth Inhibitors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins