Rat Brain Slices: An Optimum Biological Preparation for Acute Neurotoxicological Studies
The search for alternative biological preparations comprising the structural and functional complexity of the whole brain is needed for the accurate development of acute and chronic pharmacological and toxicological studies. A good, easy-to-obtain and eas
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on The three basic principles (3Rs) in animal research remain dictating the design and administration of experiments elsewhere. Whenever possible, replacement of “upper” animals (rodents and nonhuman primates) by “lower” living models (lower vertebrates
Gabriela Aguilera-Portillo, Aline Colonnello-Montero, and Marisol Maya López are authors who equally contributed to this review; therefore, they should be considered as first authors. Edgar Rangel and Abel Santamaría should both be considered as corresponding authors. Michael Aschner and Lucio Costa (eds.), Cell Culture Techniques, Neuromethods, vol. 145, https://doi.org/10.1007/978-1-4939-9228-7_10, © Springer Science+Business Media, LLC, part of Springer Nature 2019
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or invertebrates), reduction in the number of animals used to obtain the same amount and quality of information, and refinement of experimental procedures to improve animal welfare and reduce distress are all key premises to follow nowadays, especially when ethical issues are stricter every day. Therefore, the search for alternative models and platforms to improve the quality of research obeying these principles is accompanied by criteria such as the achievement of solid inferences similar to those collected from “upper” vertebrates. Despite that it is not the intention of this review to describe and discuss these principles and the issues behind them since this topic has been recently and nicely discussed in previous reports [1], basic concepts of this preparation are needed to better understand this work: the brain cortical slices represent a good ex vivo platform where a fragment of the brain is explanted and preserved either for short- or long-term studies. This preparation preserves the cellular diversity of the region (including neuronal, glial, and endothelial cells) and the many functional interactions within; therefore, brain slices are useful for both physiological and pharmacological studies. Moreover, since the slices can be preserved at the structural and functional levels for a short period of time (ranging 6–8 h) with the appropriate culture conditions [1], electrophysiological, neurochemical, and pharmacological studies carried out under these conditions represent an acute phase of study where the cytoarchitecture of the region, the complexity of cellular interactions, and the synaptic circuits remain all well preserved. Taking advantage of these properties, it is possible to conduct acute or short-term toxicological studies; in particular, for chronic or long-term studies, the organotypic cultures represent a good alternative when culture conditions (oxygen supply, pH, nutrients, etc.) are appropriate. This review provides a simple and accurate description of methods to start and perform experiments with rat cortical slices aimed to characterize endpoints of acute toxicity at biochemical and cellular levels representing the changes that can be also found in experiments with cultured cells, invertebrates, or even in in vivo experiments with
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