Neurotoxicity

Neurotoxicity is the capacity of chemical, biologic, or physical agents to cause adverse functional or structural change in the nervous system. Neurotoxicity is one of the major causes for adverse drug reactions and drug attrition during preclinical or clinical development. This leads to the importance of improving risk assessment early in the drug discovery process. In vitro assays can also be used to:

screen for improved the chemical content
mitigate the potential neurotoxicity of future drug candidates
help to limit the number of compounds that are tested in vivo
reduce time and costs associated with neurotoxicity testing
limit the impact that safety issues and withdrawal due to safety issues related to neurotoxicity

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Assessment of neurotoxicity can be accomplished by assessment of cytotoxicity to neurons, activation of astrocytes, and evaluation of modulation of calcium signaling. Mechanistic neurotoxicity can be evaluated in vitro through the use of cultured neuronal models in traditional monolayer assay format, or with 3D neuronal organoids.

Lonza offers a range of cryopreserved mouse and rat primary neuron and glia cells prepared from freshly isolated and dissociated embryonic or neonatal nervous tissue from Sprague Dawley rats or CD-1 and C57 Black mice. Lonza's portfolio also includes reliable neural media products that are optimized and tested specifically with our primary neural cells. Our serum-free neural media allows for the long-term maintenance and growth of neural cells in culture. With years of experience in primary neural cell isolation, Lonza offers ready-to use, high quality neural cells for your research. Extensive testing and optimization provides quality and performance of our neural cells with every batch produced.

Lonza and neurotoxicity

Neurotoxicity studies requires gaining understanding of individual functionality and connectivity of neurons and synapses. Multi-well Micro Array Electrode (MEA) technology provides insights on both single cell and network activity of neurons. This technology was utilized for electrophysiological assessment of neurons to determine neural activity and connectivity. In this proconvulsant neurotoxicity risk study Lonza Rat cortical neurons were assessed for functionality by measuring action potential, synchronization and oscillations on the Maestro™ MEA platform.

In vitro neurotoxicity assays based on cultured primary neural cells provide for greater predictivity. Common assays include:

Neurite outgrowth assay

Neuronal outgrowth is critical for communication between neurons, and essential for nervous system functioning, therefore it can serve as an indicator of neurotoxicity. One incubates neuronal cultures with test compounds and then stains the axon and dendrite outgrowth via ICC. Allowing for the length and number of neurites to be measured and counted using high-content imaging.

Cytotoxicity assay

Neurotoxicity be assessed by monitoring the effect of compounds on cell viability, apoptosis, and membrane integrity.

Calcium flux assay

Intracellular calcium flux can indicate neurotoxicity.

Functional Assay of Neural Activity with Cell-Based Neural Culture Models and Microelectrode Array Technology for Proconvulsant Risk Assessment in the Neutox Pilot Study

Lonza and Axion Biosystems’ poster from the 2019 SOT meeting discussing the use of primary cortical cell models and microelectrode array (MEA) technology for neurotoxicology and safety pharmacology assessment applications. Download Document