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Published on: October 27, 2014
Paclitaxel-induced Neurological Dysfunction: An In Vivo Study in Female SKH-1 Mice
Susanne Reuter1,2, Fabian Müller-Graf3, Amelie R Zitzmann3
1Institute for Experimental Surgery, University Medical Center Rostock, Rostock, Germany; susanne.reuter@med.uni-rostock.de.
Background/Aim:
Chemotherapy-induced peripheral neuropathy (CIPN) is frequent, having a lasting impact on the quality of life and is neither preventive nor do causal treatment options exist. The aim of this study was to systematically evaluate an in vivo female SKH-1 mouse model with respect to the temporal occurrence of paclitaxel-induced peripheral neurological dysfunction.
Materials And Methods:
A total of 108 female SKH-1 mice were randomly assigned to three groups, and each received six cycles of intraperitoneal injections: the treatment group received paclitaxel, the vehicle group cremophor, and the control group saline. Various neurological and behavioral tests including the von Frey Filament, RotaRod, adhesive tape removal test, and water maze test, as well as biochemical and morphological analyses, were performed.
Results:
In addition to significant performance deficits in the RotaRod test, the von Frey test showed progressive peripheral neuropathy in paclitaxel-treated mice, beginning with hyperesthesia followed by significant hypesthesia of the hind paws. Ubiquitin C-terminal hydrolase (UCH-L1) was elevated at an early stage after chemotherapy, and animals with hyperesthesia showed significantly greater condensation per axon than animals administered saline.
Conclusion:
The female SKH-1 strain developed chemotherapy-induced peripheral neuropathy after paclitaxel application. Therefore, this in vivo mouse model appears to be suitable for chemotherapy-induced peripheral neuropathy research. It could help reduce gender disparities in medicine.
