Creative Biolabs

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.

Our Services Descriptions
Neuronal Toxicity Assay Neuronal toxicity assay is mainly based on the changes in cell membrane permeability. Based on cultured neural cells, numerous in vitro neurotoxicity assays are available at Creative Biolabs.
DRG Neurons Peripheral Neurotoxicity Assay The DRG neurons neurotoxicity assay is a powerful tool for evaluating the potential neurotoxicity of drugs on sensory neurons. We can assess the viability of neurons using a range of techniques, including fluorescent dyes, mitochondrial function assays, and high-content imaging.
Neurotoxicity Assay Creative Biolabs can assess neuronal responses to drugs using neurotoxicity kits and classical neuronal growth models, as well as tests of calcium flux, oxidative stress, apoptosis, blood-brain barrier permeability and other means to monitor various sensitive biological indicators.

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:

Cat. No Product Name Cell Type
NCL200552ZP iNeu™ Human Neural Stem Cell Line iPSC-derived neural cells
NCL-2108P29 Mouse Hippocampal Neuron Cell Line HT-22 Immortalized Cell Lines
NCC20-9PZ48 C57 Brain Cortex Neurons [Mouse] Primary Cells
NCL-2103-P28 Mouse Microglia Primary Cells
NCL-7P018 iNeu™ Human iPSC-derived Microglia iPSC-derived neural cells
NCL-21P6-175 Immortalized Mouse Schwann Cell Immortalized Cell Lines
NCL-2105-P244-AM Rat Schwann Cells (IFRS1), Immortalized Immortalized Cell Lines
NCL2110P219 Green Fluorescent Tau SH-SY5Y cell Line Neurological Disease Models
NCL2110P356 Synuclein A53T Overexpressed SH-SY5Y Cell Line Neurological Disease Models
NCL2110P209 Green Fluorescent Alpha-synuclein SH-SY5Y Cell Line Neurological Disease Models
NCL2110P210 Red Fluorescent Alpha-synuclein SH-SY5Y Cell Line Neurological Disease Models
NCL2110P211 Green Fluorescent Alpha-synuclein HEK293 Cell Line Neurological Disease Models
NCL2110P212 Red Fluorescent Alpha-synuclein HEK293 Cell Line Neurological Disease Models
NCL2110P154 Mouse Retinal Ganglion Cell Line RGC-5 Immortalized Cell Lines
NCL2110P145 Mouse Retinal Ganglion Cells Primary Cells
NCL-2106-S93 Rat Immortalized Retinal Muller Cell Line rMC-1 Immortalized Cell Lines
NRZP-1122-ZP125 Rabbit Corneal Endothelial Cells Primary Cells
NCL-2105-P272-AM Immortalized Rat Retinal Pigment Epithelial Cells (BPEI-1) Immortalized Cell Lines
NCL-2103-P173 Human Retinal Pigment Epithelial Cells Primary Cells
NCL-2105-P263-AM Immortalized Human Retinal Pigment Epithelial Cells Immortalized Cell Lines
NCL-2105-P253-AM Human Corneal Endothelial Cells, Immortalized Immortalized Cell Lines

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.
In Vitro Models Advantages Limitations
Neuronal cell lines
  • Good reproducibility
  • Easier to obtain large numbers of cells
  • Proven research methodology
  • Usually derived from human body
  • The differentiation process is not comparable to the natural differentiation of normal cells. Neurons do not represent axons or dendrites and do not form functional synapses.
  • There is only one cell type and cell-cell interactions are absent.
  • Continuous cell division makes it difficult to obtain a stable population of differentiated cells.
Cerebral cortex or spinal cord neurons
  • Have spontaneous electrical activity
  • Presence of gamma-aminobutyric acid, glutamate, and cholinergic neurons
  • Preserves neuronal and glial cell interactions
  • Can be used for acute or chronic neurotoxicity testing
  • Proto-brain tissue-type structures may be disrupted.
  • There are differences in the neuronal to glial cell ratios, as well as glial cell-to-glial cell ratios, between individuals.
  • In some cases, in vitro models of the blood-brain barrier need to be included or tested separately.
  • Difficult to obtain, costly to culture, difficult to maintain in culture for long periods of time, and susceptible to contamination by glial cells.
Cerebellar granule cells
  • Almost pure population of glutamatergic neurons, with small numbers of γ-aminobutyric acid neurons also present
  • Easily accessible for assessment in single-cell toxicity assays
  • Large number of neurons
Neural stem cells
  • Highly reproducible
  • High throughput screening for drugs possible
  • Neuronal network activity can be monitored by microelectrode arrays, combined with calcium signaling
  • Controllable ratio between neurons and glial cells
  • Longer time to differentiate
  • Technically difficult
Reaggregating brain cells
  • Similar to in vivo structure and function
  • Preserve neuronal and glial cell interactions
  • Preserves synaptic and myelin structures
  • Allows electrophysiological studies
  • Not suitable for single-cell level studies
  • Interindividual differences in brain tissue size, neuron to glial cell ratio, and electrical activity
Brain organoids
  • Composed of multiple cell types that mimic in vivo structure and function
  • Cultures can last up to several months
  • Can be used to study cellular targets that mediate neurotoxicity or drug efficacy
  • Difficult to duplicate across units, not yet standardized
  • Lack of adult blood-brain barrier model
  • Integration of drug toxicity and drug metabolism in a single model
  • Accurately control local environment and mimic in vivo environment
  • Re-establishment of tissue barrier function, parenchymal tissue culture, and integration of multiple organ functions can be realized
  • Microfluidic chip is technically difficult
  • Expensive

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.

For Research Use Only. Not For Clinical Use.
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