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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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Yan Y,Sun HH,Mackinnon SE,Johnson PJ

doi

10.1016/j.expneurol.2011.06.013

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

7-14

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(11)00235-4

journal_volume

232

pub_type

杂志文章

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