Microelectrode arrays: A physiologically based neurotoxicity testing platform for the 21st century

Johnstone, Andrew F.M.; Gross, Guenter W.; Weiss, Dieter G.; Schroeder, Olaf; Gramowski, Alexandra; Shafer, Timothy J.

doi:10.1016/j.neuro.2010.04.001

Cited by 345 publications

(261 citation statements)

References 63 publications

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“…In vitro models allow a drastic reduction in the usage of animals and associated costs. They also show great promise for scaling to high throughput (Johnstone et al, 2010;Gross et al, 2006). The hypothesis of this study was that D-Met is protective against cisplatin-induced acute cytotoxicity as well as functional neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…The in vitro environment allows precise, reproducible pharmacological manipulations with no homeostatic interference from other organs. Morphological changes of neurons in the networks can be correlated optically with electrophysiological changes, and network deterioration can be followed systematically, providing a platform for rapid, quantitative screening of new chemical and pharmaceutical compounds (Johnstone et al, 2010;Novellino et al, 2011;Wu et al, 2011). Mice have been extensively used as the mammalian animal model in physiological and pharmacological experiments.…”

Section: Introductionmentioning

confidence: 99%

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d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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Cisplatin is a platinum-based chemotherapeutic agent widely used for the treatment of various types of cancer. Patients undergoing cisplatin treatment often suffer from a condition known as "chemobrain", ototoxicity, peripheral neuropathy, weight loss, nausea, vomiting, nephrotoxicity, seizures, hearing loss and tinnitus.D-Methionine (D-Met), a sulfur-containing nucleophilic antioxidant, has been shown to prevent cisplatininduced side effects in animals without antitumor interference. In this study, we have used an in vitro model of cortical networks (CNs), enriched in auditory cortex cells; to quantify cisplatin neurotoxicity and the protective effects of D-Met. Dissociated neurons from auditory cortices of mouse embryos were grown on microelectrode arrays with 64 transparent indium-tin oxide electrodes, which enabled continuous optical and electrophysiological monitoring of network neurons. Cisplatin at 0.10-0.25 mM induced up to a 200% increase in spontaneous spiking activity, while concentrations at or above 0.5 mM caused irreversible loss of neuronal activity, accompanied by cell death. Pretreatment with D-Met, at a concentration of 1.0 mM, prevented the cisplatin-induced excitation at 0.10-0.25 mM, caused sustained excitation without occurrence of cell death at 0.5 mM, and delayed cell death at 0.75 mM cisplatin. L-Methionine, the optical isomer, showed lower potency and less efficacy than D-Met, was less protective against 0.1 mM cisplatin, and proved ineffective at a concentration of 0.5 mM cisplatin. Pre-exposure time of D-Met was associated with the protective effects at 0.1 and 0.5 mM cisplatin, with longer pre-exposure times exhibiting better protection. This study quantifies as a function of concentration and time that D-Met protects central nervous system tissue from acute cisplatin toxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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“…Primary cortical cultures consist of a mixed population of multiple types of (excitatory and inhibitory) neurons as well as supportive cells (e.g., astrocytes) that form functional neuronal networks. These primary cultures are well characterized, widely accepted, easily cultured and recapitulate many aspects of nervous system function (for review, see Johnstone et al, 2010;de Groot et al, 2013). While electrophysiological assessment of ion channel or neurotransmitter receptor function is ideally suited to investigate chemically-induced changes in neuronal function and transmission (de Groot et al, 2013), it may be too endpointspecific and not taking into account the net effect on the neuronal network.…”

Section: Tablementioning

confidence: 99%

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

et al. 2017

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A B S T R A C TExposure to tricresyl phosphates (TCPs), via for example contaminated cabin air, has been associated with health effects including the so-called aerotoxic syndrome. While TCP neurotoxicity is mainly attributed to ortho-isomers like tri-ortho-cresyl phosphate (ToCP), recent exposure and risk assessments indicate that ToCP levels in cabin air are very low. However, the neurotoxic potential of non-ortho TCP isomers and TCP mixtures is largely unknown. We therefore measured effects of exposure (up to 48 h) to different TCP isomers, mixtures and the metabolite of ToCP (CBDP: cresyl saligenin phosphate) on cell viability and mitochondrial activity, spontaneous neuronal electrical activity, and neurite outgrowth in primary rat cortical neurons.The results demonstrate that exposure to TCPs (24-48 h, up to 10 mM) increases mitochondrial activity, without affecting cell viability. Effects of acute TCP exposure (30 min) on neuronal electrical activity are limited. However, electrical activity is markedly decreased for the majority of TCPs (10 mM) following 48 h exposure. Additional preliminary data indicate that exposure to TCPs (48 h, 10 mM) did not affect the number of neurites per cell or average neurite length, except for TmCP and the analytical TCP mixture (Sigma) that induced a reduction of average neurite length.The combined neurotoxicity data demonstrate that the different TCPs, including ToCP, are roughly equipotent and a clear structure-activity relation is not apparent for the studied endpoints. The noobserved-effect-concentrations (1 mM) are well above current exposure levels indicating limited neurotoxic health risk, although exposures may have been higher in the past. Moreover, prolonged and/or repeated exposure to TCPs may exacerbate the observed neurotoxic effects, which argues for additional research.

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“…Microelectrode array (MEA) recordings are used to measure mainly spontaneous network activity of cultured neurons (Keefer et al, 2001, Gramowski et al, 2000and Gopal, 2003Johnstone et al, 2010). However, using specific agonists and antagonists of a receptor, including NMDAR, MEA technology can be used to measure evoked activity, including glutamatergic receptor function .…”

Section: How It Is Measured or Detectedmentioning

confidence: 99%

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

Sachana

Munn

Bal‐Price

2016

OECD Series on Adverse Outcome Pathways

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Microelectrode arrays: A physiologically based neurotoxicity testing platform for the 21st century

Cited by 345 publications

References 63 publications

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

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