Neurotoxicity of Seven MEIC Chemicals Evaluated in Organotypic Cultures of Chick Embryonic Dorsal Root Ganglia

The neurotoxic effects of seven selected Multicenter Evaluation of In Vitro Cytotoxicity programme chemicals (methanol, ethanol, isopropanol, sodium chloride, potassium chloride, iron [II] sulphate and chloroform) were evaluated in organotypic cultures of chick embryonic dorsal root ganglia (DRG), maintained in a soft agar culture medium. Two growth parameters of neurite outgrowth from the ganglia — the mean radial length of neurites and the area of neurite outgrowth — were used to evaluate the toxicities of the chemicals. Dose-dependent decreases of both parameters were observed in all experiments. IC50 values (the concentration causing 50% inhibition of growth) were calculated from the dose-response curves established at three time-points during culture, i.e. 24, 48 and 72 hours. The lowest toxic effect was observed in cultures exposed to methanol (the IC50 ranging from 580mM to 1020mM). The highest toxic effect was observed in cultures exposed to iron (II) sulphate (the IC50 ranging from 1.2mM to 1.7mM). The results of other recent experiments suggest that organotypic cultures of DRG can be used during in vitro studies on target organ toxicity within the peripheral nervous system. Moreover, these cultures preserve the internal organisation of the tissue, maintain intercellular contacts, and thus reflect the in vitro situation, more precisely than other cell cultures.

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Reversal by NGF of cytostatic drug-induced reduction of neurite outgrowth in rat dorsal root ganglia in vitro

Brain Research ◽

10.1016/0006-8993(94)91873-2 ◽

1994 ◽

Vol 640 (1-2) ◽

pp. 195-204 ◽

Cited By ~ 47

Author(s):

Pierre N.M. Konings ◽

W. Karolien Makkink ◽

Anton M.L. van Delft ◽

Ge´S.F. Ruigt

Keyword(s):

Neurite Outgrowth ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Cytostatic Drug ◽

Drug Induced

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Oncomodulin derived from regeneration-associated macrophages in dorsal root ganglia promotes axon regeneration in the spinal cord

10.1101/2021.12.28.474322 ◽

2021 ◽

Author(s):

Min Kwon ◽

Yeojin Seo ◽

Hana Cho ◽

Jihye Choi ◽

Hyung Soon Kim ◽

...

Keyword(s):

Spinal Cord ◽

Neurite Outgrowth ◽

Dorsal Root Ganglia ◽

Axonal Regeneration ◽

Dorsal Root ◽

Axon Regeneration ◽

Signal Sequence ◽

Drg Neurons ◽

Cord Injury

Preconditioning peripheral nerve injury enhances axonal regeneration of dorsal root ganglia (DRG) neurons in part by driving pro-regenerative perineuronal macrophage activation. How these regeneration-associated macrophages influence the neuronal capacity of axon regeneration remains elusive. The present study reports that oncomodulin (ONCM) is an effector molecule derived from the regeneration-associated macrophages. ONCM was highly upregulated in DRG macrophages following preconditioning injury and necessary for the preconditioning-induced neurite outgrowth. ONCM-deficient macrophages failed to generate neurite outgrowth activity of the conditioned medium in the in vitro model of neuron-macrophage interaction. CCL2/CCR2 signaling is an upstream regulator of ONCM since the ONCM upregulation was dependent on CCR2 and CCL2 overexpression-mediated conditioning effects were attenuated in ONCM-deficient mice. Direct application of ONCM potently increased neurite outgrowth in cultured DRG neurons by activating a distinct gene set, particularly neuropeptide-related genes. AAV-mediated overexpression of ONCM construct with the signal sequence increased neuronal secretion of ONCM and enhanced neurite outgrowth in an autocrine manner. For a clinically relevant approach, we developed a nanogel-mediated system for localized delivery of recombinant ONCM to DRG tissue. Electrostatic encapsulation of ONCM by a reducible epsilon-poly(L-lysine)-nanogel (REPL-NG) resulted in a slow release of ONCM allowing sustained bioactivity. Intraganglionic injection of REPL-NG/ONCM complex achieved a remarkable long-range axonal regeneration beyond spinal cord lesion, surpassing the extent expected from the preconditioning effects. The NG-mediated ONCM delivery could be exploited as a therapeutic strategy for promoting sensory axon regeneration following spinal cord injury.

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Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2010.06.039 ◽

2010 ◽

Vol 398 (1) ◽

pp. 79-85 ◽

Cited By ~ 7

Author(s):

K.T. Wright ◽

R. Seabright ◽

A. Logan ◽

A.J. Lilly ◽

F. Khanim ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Neurite Outgrowth ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Kinase Activity ◽

Nucleoside Diphosphate Kinase ◽

Nerve Growth ◽

Dorsal Root Ganglia Neurons

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Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro.

Acta Biomaterialia ◽

10.1016/j.actbio.2021.06.049 ◽

2021 ◽

Author(s):

Jessica L. Funnell ◽

Alexis M. Ziemba ◽

James F. Nowak ◽

Hussein Awada ◽

Nicos Prokopiou ◽

...

Keyword(s):

Magnetic Field ◽

Iron Oxide ◽

Neurite Outgrowth ◽

Iron Oxide Nanoparticles ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Electrospun Fibers ◽

Oxide Nanoparticles ◽

Field Stimulation

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CYTOLOGICAL STUDIES OF ORGANOTYPIC CULTURES OF RAT DORSAL ROOT GANGLIA FOLLOWING X-IRRADIATION IN VITRO

The Journal of Cell Biology ◽

10.1083/jcb.32.2.467 ◽

1967 ◽

Vol 32 (2) ◽

pp. 467-496 ◽

Cited By ~ 55

Author(s):

Edmund B. Masurovsky ◽

Mary Bartlett Bunge ◽

Richard P. Bunge

Keyword(s):

Endoplasmic Reticulum ◽

Dorsal Root Ganglia ◽

Satellite Cells ◽

Dorsal Root ◽

Nervous Tissue ◽

X Rays ◽

Organotypic Cultures ◽

X Irradiation

Long-term organotypic cultures of rat dorsal root ganglia were exposed to a single 40 kR dose of 184 kvp X-rays and studied in the living and fixed states by light or electron microscopy at 1–14 day intervals thereafter. Within the first 4 days following irradiation, over 30% of the neurons display chromatolytic reactions (eccentric nuclei, peripheral dispersal of Nissl substance, central granular zone) as well as abnormal nucleolar changes and dissociation of ribosomes from endoplasmic reticulum cisternae. Some satellite cells undergo retraction or acute degeneration, leaving only basement membrane to cover the neuron in these areas. 8 days after irradiation, neurons also exhibit (a) areas in which ribosomes are substantially reduced, (b) regions of cytoplasmic sequestration, (c) extensive vacuolization of granular endoplasmic reticulum and Golgi complex, and (d) diversely altered mitochondria (including the presence of ribosome-like particles or association with abnormal glycogen and lipid deposits). Nucleolar components become altered or reoriented and may form abnormal projections and ringlike configurations. Sizeable areas of the neuronal soma are now denuded of satellite cells; underlying these areas, nerve processes are found abnormally invaginated into the neuronal cytoplasm. By the 14th day following irradiation, most neurons display marked degenerative changes including extensive regions of ribosome depletion, sequestration, vacuolization, autolysis, and, in some areas, swirls of filaments, myelin figures, and heterogeneous dense bodies. These observations demonstrate that X-irradiation produces profound cytopathological changes in nervous tissue isolated from the host and that many of these changes resemble the effects of radiation on nervous tissue in vivo.

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