RECOMBINANT HUMAN GLIAL GROWTH-FACTOR 2 (RHGGF-2) IMPROVES FUNCTIONALRECOVERY OF CRUSHED PERIPHERAL-NERVE (A DOUBLE-BLIND-STUDY)

This in vivo double-blind study evaluated the effect of recombinant hu man glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the rec overy of motor function of rat sciatic nerve following crush injury. S eventy 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 l oad for 2 h over a 5 mm segment of the sciatic nerve. Group III was tr eated with I mg/kg rhGGF2, via subcutaneous injection one day before n erve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery w as assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum l ongus (EDL) muscle. Recovery of nerve function was evident at day II a fter crush in the rhGGF2-treated animals, whereas the nerves in contro ls were still paralyzed. The rhGGF2-treated animals showed a significa nt improvement of the SFI between days 11-21 postoperatively when comp ared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant diff erence at 40 to 70 Hz stimulus frequencies on day 4. Correlation analy sis showed that tetanic contractile force had a linear correlation wit h the SFI. Histologic assessment indicated that the rhGGF2-treated ani mals 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 inducin g neurotrophic factors essential to neuronal maintenance and repair. ( C) 1998 Elsevier Science Ltd. All rights reserved.