Evaluation Models and Applications of Drug Neurotoxicity

Drug neurotoxicity refers to drug-induced damage to the function and/or structure of the nervous system. Neurotoxicity is one of the adverse drug reactions and an important aspect of preclinical safety evaluation of drugs. In general, models for studying and evaluating neurotoxicity mainly refer to in vitro models and in vivo models. Only a single in vivo model or in vitro model cannot evaluate drug neurotoxicity in a complete and comprehensive way, so for different drugs, it is necessary to choose appropriate methods and model combinations for comprehensive evaluation in order to draw accurate and reliable conclusions.

In recent years, with the advancement of technology, the application of new models has provided new possibilities for neurotoxicity studies. Creative Biolabs introduces a variety of in vivo and in vitro models for neuroscience research, which will provide a reference for model selection in future drug neurotoxicity studies. As a partner, we offer the following related services to help clients perform neurotoxicity studies.

Why are Appropriate Models Needed for Drug Neurotoxicity Studies?

Symptoms of drug neurotoxicity include dizziness, vomiting, seizures and sensory disturbances. Some drugs may even cause irreversible damage to neurons, so studies of drug neurotoxicity are necessary to guide clinical dosage adjustment and suggest that special attention should be paid to possible neurotoxicity when applying such drugs.

Common neurotoxic drugs include cisplatin, doxorubicin, vincristine and other chemotherapeutic drugs, nitrous oxide, midazolam, isoflurane and other anesthetics, as well as non-steroidal anti-inflammatory drugs, diuretics, central nervous system stimulants, antiepileptic drugs and so on. In addition, certain antibiotics are potentially neurotoxic while treating bacterial infections, e.g., polymyxins, β-lactams, and others.

Therefore, it is important to find suitable neurotoxicity models to study the effects of drugs on the human nervous system.

Models for studying and evaluating neurotoxicity mainly refer to in vitro models and in vivo models.

• In vitro models include 2D single-cell cultures, 3D multi-cell cultures, and organotypic cultures.
• In vivo models include traditional mammalian models and non-mammalian models.

We are proud of offering a diverse array of high-quality brain cells lines used as excellent in vitro models for research of toxicity screening, including but not limited to:

In Vitro Models for Neurotoxicity Studies

The advantages of in vitro models over in vivo models are the ability to observe different cells and cellular interrelationships within the nervous system at the microscopic level, and to detect key cellular alterations, including metabolism, genes, and proteins, using relatively simple techniques and methods. In vitro models of varying complexity have their own unique strengths and limitations, and can be used as screening tools for potential neurotoxicants, as well as for mechanistic studies of cellular, biochemical and molecular effects of neurotoxicants at different levels.

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In Vivo Models for Neurotoxicity Studies

The primary endpoints to be assessed in neurotoxicity studies, which include five areas, are structural or neuropathology, neurophysiology, neurochemistry, neurobehavioral, and neurodevelopmental. With the introduction of the 3R principles of Reduction, Replacement, and Refinement, non-mammalian models have received increasing attention. Although non-mammals differ greatly in organization from humans, recent genetic techniques have shown that certain non-mammals possess a large number of human homologous conserved genes and share common neurophysiological properties with humans, which makes them very promising for studying neurotoxicity mechanisms.

• The nervous system of nematodes contains almost all known signals and neurotransmitters in vertebrates, such as acetylcholine, dopamine, 5-hydroxytryptamine, glutamate, GABA, etc. The mapping of the complete neuronal network and synaptic connections of nematodes has been completed.
• The telencephalon, mesencephalon, and midbrain of the mammalian brain have their counterparts in zebrafish. In addition, zebrafish and mammals share common developmental processes such as neural development, axon formation, and associated genetic signals.
• Drosophila has many molecular pathways critical for responding to neurotoxic drugs. In neurobiology, Drosophila is similar to humans in basic cellular processes such as synapse formation, neurotransmitter transmission, membrane transport, and neuronal death, as well as in various aspects of behavior such as sensation, locomotion, and learning memory.

Identifying genes or pathways conserved in non-mammalian and mammalian species will help in drug neurotoxicity target discovery and inhibitor development, and the future direction lies in extrapolating the quantitative efficacy relationships observed in non-mammals to the human body to make non-mammalian in vivo studies more informative for in vivo studies in humans.

With the development of neuroscience, neurobiology and cell culture technology, Creative Biolabs is exploring more suitable models and methods for neurotoxicity evaluation.

Related Scientific Resources

Neurotoxins

Animal Related Studies in Neurosciences