Evaluation of peripheral nerve regeneration via in vivo serial transcutaneous imaging using transgenic Thy1-YFP mice

• Published in: Experimental neurology Vol. 232; no. 1; pp. 7 - 14
• Main Authors: Yan, Ying, Sun, Hank H., Mackinnon, Susan E., Johnson, Philip J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-11-2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Conditioning injury; Disease Models, Animal; Dose-Response Relationship, Drug; FK-506; GFAP-GDNF (glial fibrillary acidic protein); Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Fibrillary Acidic Protein; Immunosuppressive Agents - pharmacology; Injuries of the nervous system and the skull. Diseases due to physical agents; Live imaging; Medical sciences; Mice; Mice, Transgenic; Nerve Crush; Nerve regeneration; Nerve Regeneration - drug effects; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Peripheral Nerve Injuries - physiopathology; Peripheral Nerves - drug effects; Peripheral Nerves - physiopathology; Tacrolimus - pharmacology; Thy-1 Antigens - genetics; Thy-1 Antigens - metabolism; Thy1-YFP mouse; Traumas. Diseases due to physical agents; Treatment Outcome; Nerve crush; Thy1-YFP mouse; GFAP-GDNF (glial fibrillary acidic protein); FK-506; Live imaging; Conditioning injury; Nerve regeneration; Evaluation; Peripheral nerve; Nervous system diseases; Glial fibrillary acidic protein; Rodentia; Regeneration; Vertebrata; Mammalia; Mouse; Tacrolimus; Animal; Glial cell line derived neurotrophic factor; Conditioning
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2011.06.013

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.
► We evaluate axonal regeneration in Thy1-YFP mice via
in vivo transcutaneous imaging. ► Animals undergo saphenous nerve crush, various FK-506 regimens, and
in vivo imaging. ► Animals with central GDNF overexpression are assessed. ► Daily FK-506 with preload accelerates axonal regeneration after crush injury. ► Central GDNF overexpression impedes axonal regeneration after crush injury.