gms | German Medical Science

Objective: Granulocyte-colony stimulating growth factor (G-CSF) has been observed to have direct protective effects on neurons. Besides its neuroprotecting effect, G-CSF fosters the formation of vessels after brain ischemia and improves the recovery of sensorimotor and cognitive functions in experimental models and in humans after stroke. In the present study, possible anti-apoptotic effects of G-CSF on nerves’ α-motoneurons after sciatic nerve lesion in rats were evaluated.

Methods: Traumatic lesion has been applied to the right sciatic nerve in 48 rats. Twenty-four animals were treated with G-CSF and 24 animals were treated with intravenous glucose 5%-solution serving as control group. For histological analysis, spinal cord sections of 6 animals of both groups were removed at day 1, day 4, day 7 and day 14. α-motoneurons of both sides were counted and investigated for expression of cholin-acetyltransferase (ChAT), granulocyte-colony stimulating factor receptor (G-CSFR), and the proteins Bcl-2 and Bax. To proof evidence of anti-apoptotic effects within α-motoneurons, fluorescence double-staining was performed for ChAT/Bcl-2, ChAT/Bax and ChAT/G-CSFR.

Results: Counting of α-motoneurons revealed a significantly smaller number of ChAT-stained motoneurons on the lesioned side in animals of the control group at day 1 to day 14 (p < 0.05). In animals that were treated with G-CSF, numbers of α-motoneurons were equal. Additionally, significantly less α-motoneurons with Bcl-2- and G-CSFR-expression were counted on the lesioned side in animals of the control group (p < 0.05). Compatible with this, Bax-expression in animals of the control group was significantly higher on the lesioned side (p < 0.05). Fluorescence double-staining in α-motoneurons was positive for ChAT/Bcl-2, ChAT/Bax as well as for Chat/G-CSFR.

Conclusion: The application of G-CSF after nerve lesion seemed to have a strong neuroprotective effect in α-motoneurons of the sciatic nerve section. It was shown that the number of motoneurons decreased in animals of the control group whereas no difference was observed in animals treated with G-CSF. Concordantly, apoptotic effects were shown by decreased Bcl-2 expression and increased pro-apoptotic Bax-expression in motoneurons of animals treated with G5%-solution. These results indicate that the application of G-CSF contributes to anti-apoptotic effects after traumatic nerve lesion. The relevance of G-CSF, the precise mode of action as well the impact of these findings in the clinical situation will have to be examined in further studies.