The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration.
OBJECTIVE
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.
Magill
Christina K
CK
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Moore
Amy M
AM
Yan
Ying
Y
Tong
Alice Y
AY
MacEwan
Matthew R
MR
Yee
Andrew
A
Hayashi
Ayato
A
Hunter
Daniel A
DA
Ray
Wilson Z
WZ
Johnson
Philip J
PJ
Parsadanian
Alexander
A
Myckatyn
Terence M
TM
Mackinnon
Susan E
SE
D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009045:Motor Endplate / Q000737:chemistry*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D012584:Sciatic Nerve / Q000737:chemistry*
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor