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in vitro toxicology

Neurotoxicity

Neurotoxicity occurs when neurotoxins affect the normal activity of the nervous system and ultimately damage nervous tissue. Possible symptoms can include motor function and co-ordination issues, loss of memory, vision, and/or mental function, obsessive and/or compulsive behaviors, delusions, seizures, headache, cognitive and behavioral problems. Neurotoxicity can be linked to exposure from certain chemotherapy/radiation therapies, heavy metals, pesticides, food additives, industrial solvents, cleaning products and drug therapies.

The deleterious effects of neurotoxins may not become clinically apparent for some time following exposure. There is particular concern regarding low levels of environmental chemicals and their effects on fetal development, on the behavior or development of children or the development of neurodegenerative diseases in adults (e.g., Parkinson’s disease and Alzheimer’s disease).

Neurological function and behavioral effects are typically evaluated through in vivo animal models of acute and repeat dose preclinical toxicity studies. With the onset of REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) legislation, and the cost and ethical issues associated with animal testing, there is a considerable push to identify new in vitro methods which are able to predict neurotoxicity in humans.

Cyprotex offers in vitro cell based assays to study neurite outgrowth using high content imaging and electrophysiological effects using high throughput microelectrode array.

Neurite Outgrowth

  • The function of the nervous system depends on communication between neurons via neurites (axons and dendrites). Neurite outgrowth forms an essential stage in this communication process.
  • Neurite outgrowth is a useful endpoint for the detection of neurotoxicity, nervous system development disorders and can also be used in drug discovery to develop new therapies for neurodegenerative diseases.
  • Cyprotex offers neurite outgrowth assessment using high content imaging technology.

Find out more about our neurite outgrowth service

eCiphr®Neuro and eCiphr®Neuro-Human

  • Cyprotex’s eCiphr®Neuro and eCiphr®Neuro-Human cell-based assay uses high throughput 48 well microelectrode array (MEA) recordings to monitor electrophysiological activity.
  • Our original eCiphr®Neuro assay uses primary cultures of rat cortical neurons. More recently, eCiphr®Neuro-Human has been introduced which uses FUJIFILM Cellular Dynamics, Inc. (FCDI) human iPSC-derived glutamatergic neurons (iCell GlutaNeurons) co-cultured with human iPSC-derived astrocytes (iCell Astrocytes).
  • Neurons grown on microelectrode array instruments recapitulate many features of neurons in vivo, including spontaneous activity (spiking and bursting), plasticity, organization and responsiveness to a wide range of neurotransmitters and pharmacological agonists/antagonists1.
  • This technology provides a unique in vitro system for drug discovery, neurotoxicity assessment, seizure prediction and disease modeling2.
  • Spike rate, burst duration, interspike interval and changes in synchrony/organization are typically reported.

Find out more about eCiphr®Neuro

Find out more about eCiphr®Neuro-Human

References

1 Robinette BL et al., (2011) In vitro assessment of development neurotoxicity: use of microelectrode arrays to measure functional chnages in neuronal network ontogeny. Front Neuroeng 4; Article 1

2 Bradley JA et al., (2018) In vitro screening for seizure liability using microelectrode array technology. Toxicol Sci 163(1); 240-253

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