Promoting effect of nerve growth factor on sciatic nerve regeneration after the crush injury

Bojun YUAN; Guocai LU; Junping LIU; Guanren ZHAO; Hao WU

ABSTRACT

BACKGROUND:

Besides being a basic growth factor crucial to maintain and promote the development, differentiation and survival of the central nervous system, nerve growth factor(NGF) also plays an important role in the repair of injured peripheral nerves.

OBJECTIVE:

To investigate the effect of the muscular injection of NGF on the regeneration and functional recovery of rat sciatic nerve after crush injury.

DESIGN:

A randomized controlled pilot study in rats with repeated observation and measurement.

SETTING:

Center for new drug evaluation in a military medical university.MATERIALS This study was performed in the Center for New Drug Evaluation, Department of Basic Medicine, Second Military Medical University during the period from July 1999 to March 2000, using 40 SD rats weighing 200 to 250 g(of either sex of half number) provided by the Sino-British SIPPR/BK Lab Aninal Ltd (Shanghai).

METHODS:

Forty rats were randomized into high-, mid- and low-dose NGF treatment groups, normal control group and model control group. The sciatic nerves were clamped at 6 nm distal to the sciatic notch to induce a 4-mm-wide area of crush injury. In the high-, mid-; and low-dose NGF groups, the rats were given NGF at 8, 4 and 2 μg/kg per day(corresponding to 1.6 × 10 3, 8 × 10 2 and 4 × 10 2 IU/kg per day) respectively via the muscular injection for 56 consecutive days.(NCVs) and sciatic function index(SFI) at different time points after the

RESULTS:

Compared with that of the model control group, the NCVs significantly increased in the high-dose NGF group 35 and 56 days after the injury,and in the mid-dose NGFgroup at 35 days(t=2.32-5.14, P ＜0.05-0.01 ). The SFIs significantly increased in all NGF-treated groups at 14 days ( t = 2. 29-6.28, P ＜ 0.05-0.01 ), with the recovery most conspicuous in high-dose NGF group; No significant difference in the SFIs was found between the NGF-treated groups on the 56th day. Morphological examination of the tissues identified no significant difference in the nerve myelin sheaths and axons in NGF-treated groups as compared with the normal control group,while in the model control group, myelin sheath dislocation with unclear microstructure was observed, accompanied by Schwann cell degeneration and necrosis.

CONCLUSION:

NGF promotes the repair of the damaged nerve myelin sheath and axon and stimulates nerve fiber regeneration and function recovery of the crushed rat sciatic nerves.