Impairment of Retrograde Neuronal Transport in Oxaliplatin-Induced Neuropathy Demonstrated by Molecular Imaging
Impairment of Retrograde Neuronal Transport in Oxaliplatin-Induced Neuropathy Demonstrated by Molecular Imaging
复制标题
DOI：
10.1371/journal.pone.0045776
复制
发表时间：
2012-09-20
期刊：
影响因子：
3.7
通讯作者：
Bredow, Sebastian
中科院分区：
文献类型：
--
作者：
Schellingerhout, Dawid;LeRoux, Lucia G.;Bredow, Sebastian
Background and Purpose: The purpose of our study was to utilize a molecular imaging technology based on the retrograde axonal transport mechanism (neurography), to determine if oxaliplatin-induced neurotoxicity affects retrograde axonal transport in an animal model.Materials and Methods: Mice (n = 8/group) were injected with a cumulative dose of 30 mg/kg oxaliplatin (sufficient to induce neurotoxicity) or dextrose control injections. Intramuscular injections of Tetanus Toxin C-fragment (TTc) labeled with Alexa 790 fluorescent dye were done (15 ug/20 uL) in the left calf muscles, and in vivo fluorescent imaging performed (0-60 min) at baseline, and then weekly for 5 weeks, followed by 2-weekly imaging out to 9 weeks. Tissues were harvested for immunohistochemical analysis.Results: With sham treatment, TTc transport causes fluorescent signal intensity over the thoracic spine to increase from 0 to 60 minutes after injection. On average, fluorescence signal increased 722%+/-117% (Mean+/-SD) from 0 to 60 minutes. Oxaliplatin treated animals had comparable transport at baseline (787%+/-140%), but transport rapidly decreased through the course of the study, falling to 363%+/-88%, 269%+/-96%, 191%+/-58%, 121%+/-39%, 75%+/-21% with each successive week and stabilizing around 57% (+/-15%) at 7 weeks. Statistically significant divergence occurred at approximately 3 weeks (p
