Embryonic Rat Dorsal Root Ganglia Organotypic Culture

Rat Dorsal Root Ganglia (DRG) explants from 15-day-old embryos (E15) were proposed as a model for studying peripheral neuropathy induced by drugs belonging to different classes. The parameter measured at each time point (24 hours after the drug treatment) was the length of longest neurite of each DRG evaluated by the program Image J in the control culture and after exposure to a drug. Drug-induced neurotoxicity assessment was based on the ability of E15 DRG explants to measure an outgrowth of neurites (length) when exposed to NGF and at the same time to a toxic substance (drug). E15 DRG represents a suitable model for assessing the neurotoxicity of antineoplastic drugs because in vivo DRG are the main target of several neurotoxic drugs and the concentrations of the drugs used to elicit changes in this in vitro model were, in general, comparable to those achievable in vivo.

The model has been tested treating DRG cultures with two antineoplastic drugs (paclitaxel and oxaliplatin) belonging to two different classes of antineoplastic agents and known to be both neurotoxic in clinical use and in animal models. DRG has been treated with concentrations comparable to those achievable in vivo. Neurotoxic drug concentrations induced a reduction of neurite length higher than 50% respect to control that represents the cut-off value of the test. The results obtained confirmed the neurotoxicity evidenced with the same drugs in published rat and mouse in vivo models. Intended purpose of the test method could be relevant to regulatory and scientific neurotoxicity testing for antineoplastic drugs in industry-driven compounds early screening and discovery.