title: Evaluation of peripheral nerve regeneration via in vivo serial transcutaneous imaging using transgenic Thy1-YFP mice.
abstract: This study uses the saphenous nerve crush model in Thy1-YFP mice and serial transcutaneous imaging to evaluate the rate of nerve regeneration under various FK-506 (tacrolimus) dosing regimens and in the presence of transgenic overexpression of glial cell line-derived neurotrophic factor (GDNF). Thy1-YFP transgenic mice received saphenous nerve crush and were monitored for axonal regeneration via transcutaneous imaging for 7 days. Group A received no FK-506. Groups B and C received FK-506 at 2 or 0.5 mg/kg/day, starting three days before injury (preload). Groups D and E received FK-506 at 2 or 0.5 mg/kg/day, starting on the day of injury. Group F consisted of double transgenic mice with central overexpression of GDNF by CNS astrocytes (GFAP-GDNF/Thy1-YFP). Length and rate of axonal regeneration were measured and calculated over time. Regardless of concentration, FK-506 preload (Groups B and C) improved length and rate of axonal outgrowth compared with controls (Group A) and no preload (Groups D and E). Surprisingly, central overexpression of GDNF (GFAP-GDNF) delayed and stunted axonal outgrowth. Saphenous nerve crush in Thy1-YFP mice represents a viable model for timely evaluation of therapeutic strategies affecting the rate of nerve regeneration. FK-506 administered three days prior to injury accelerates axonal regeneration beyond injury conditioned regeneration alone and may serve as a reliable positive control for the model. GDNF overexpression in the CNS impedes early axonal outgrowth.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8238, St. Louis, MO 63110, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Hank H
authors.initials: HH
authors.lastname: Sun
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mackinnon
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology*; D016559:Tacrolimus / Q000494:pharmacology*; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D018800:Thy-1 Antigens; C528900:glial fibrillary astrocytic protein, mouse; D016559:Tacrolimus