The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration.

Abstract

OBJECT:

Glial cell line-derived neurotrophic factor (GDNF) has potent survival effects on central and peripheral nerve populations. The authors examined the differential effects of GDNF following either a sciatic nerve crush injury in mice that overexpressed GDNF in the central or peripheral nervous systems (glial fibrillary acidic protein [GFAP]-GDNF) or in the muscle target (Myo-GDNF).

METHODS:

Adult mice (GFAP-GDNF, Myo-GDNF, or wild-type [WT] animals) underwent sciatic nerve crush and were evaluated using histomorphometry and muscle force and power testing. Uninjured WT animals served as controls.

RESULTS:

In the sciatic nerve crush, the Myo-GDNF mice demonstrated a higher number of nerve fibers, fiber density, and nerve percentage (p < 0.05) at 2 weeks. The early regenerative response did not result in superlative functional recovery. At 3 weeks, GFAP-GDNF animals exhibit fewer nerve fibers, decreased fiber width, and decreased nerve percentage compared with WT and Myo-GDNF mice (p < 0.05). By 6 weeks, there were no significant differences between groups.

CONCLUSIONS:

Peripheral delivery of GDNF resulted in earlier regeneration following sciatic nerve crush injuries than that with central GDNF delivery. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury.

• Authors: Christina K Magill, Amy M Moore, Ying Yan, Alice Y Tong, Matthew R MacEwan, Andrew Yee, Ayato Hayashi, Daniel A Hunter, Wilson Z Ray, Philip J Johnson, Alexander Parsadanian, Terence M Myckatyn, Susan E Mackinnon
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 113 Issue 1 Pg. 102-9 (Jul 2010) ISSN: 1933-0693 [Electronic] United States
• PMID: 19943736 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Gdnf protein, mouse
• Glial Cell Line-Derived Neurotrophic Factor

Topics

• Animals
• Glial Cell Line-Derived Neurotrophic Factor (pharmacology)
• Isometric Contraction (drug effects)
• Mice
• Mice, Transgenic
• Motor Endplate (chemistry)
• Nerve Crush
• Nerve Regeneration (drug effects)
• Sciatic Nerve (chemistry)