ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Editor's Highlight: Multiparametric Image Analysis of Rat Dorsal Root Ganglion Cultures to Evaluate Peripheral Neuropathy-Inducing Chemotherapeutics.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The Efficacy of Acupuncture in Chemotherapy-Induced Peripheral Neuropathy: Systematic Review and Meta-Analysis.Integrative cancer therapiesPooled it
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- Knockdown siRNA targeting GPR55 reveals significant differences between the anti-inflammatory actions of KLS-13019 and cannabidiol.Research square · 2024Article
- The potential neuroprotective effects of cannabinoids against paclitaxel-induced peripheral neuropathy:Frontiers in pharmacology · 2024Article
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- Blockade of Cholecystokinin Type 2 Receptors Prevents the Onset of Vincristine-Induced Neuropathy in Mice.Pharmaceutics · 2022Article
- Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons.Biomolecules · 2022Article
- Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improveBioactive materials · 2022Article
- A Brief Review of In Vitro Models for Injury and Regeneration in the Peripheral Nervous System.International journal of molecular sciences · 2022Review
- Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy.Toxics · 2021Review
- Comparative Analysis of Chemotherapy-Induced Peripheral Neuropathy in Bioengineered Sensory Nerve Tissue Distinguishes Mechanistic Differences in Early-Stage Vincristine-, Cisplatin-, and Paclitaxel-Induced Nerve Damage.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Berberine Alleviate Cisplatin-Induced Peripheral Neuropathy by Modulating Inflammation SignalFrontiers in pharmacology · 2021Article
- Acute in vitro effects on embryonic rat dorsal root ganglion (DRG) cultures by in silico predicted neurotoxic chemicals: Evaluations on cytotoxicity, neurite length, and neurophysiology.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Modeling chemotherapy induced peripheral neuropathy (CIPN) in vitro: Prospects and limitations.Experimental neurology · 2020Review
- A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models.Toxicologic pathology · 2020Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a major, dose-limiting adverse effect experienced by cancer patients. Advancements in mechanism-based risk mitigation and effective treatments for CIPN can be aided by suitable in vitro assays. To this end, we developed a multiparametric morphology-centered rat dorsal root ganglion (DRG) assay. Morphologic alterations in subcellular structures of neurons and non-neurons were analyzed with an automated microscopy system. Stains for NeuN (a neuron-specific nuclear protein) and Tuj-1 (β-III tubulin) were used to identify neuronal cell nuclei and neuronal cell bodies/neurites, respectively. Vimentin staining (a component of Schwann cell intermediate filaments) was used to label non-neuronal supporting cells. Nuclei that stained with DAPI, but lacked NeuN represented non-neuronal cells. Images were analyzed following 24 h of continuous exposure to CIPN-inducing agents and 72 h after drug removal to provide a dynamic measure of recovery from initial drug effects. Treatment with bortezomib, cisplatin, eribulin, paclitaxel or vincristine induced a dose-dependent loss of neurite/process areas, mimicking the 'dying back' degeneration of axons, a histopathological hallmark of clinical CIPN in vivo. The IC50 for neurite loss was within 3-fold of the maximal clinical exposure (Cmax) for all five CIPN-inducing drugs, but was >4- or ≥ 28-fold of the Cmax for 2 non-CIPN-inducing agents. Compound-specific effects, eg, neurite fragmentation by cisplatin or bortezomib and enlarged neuronal cell bodies by paclitaxel, were also observed. Collectively, these results support the use of a quantitative, morphologic evaluation and a DRG cell culture model to inform risk and examine mechanisms of CIPN.
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