ExplantAnalyzer: An advanced automated neurite outgrowth analysis evaluated by means of organotypic auditory neuron explant cultures.

Automated image analysis High throughput MATLAB script Neurite outgrowth Organotypic explant culture Spiral ganglion neuron culture

Journal

Journal of neuroscience methods
ISSN: 1872-678X
Titre abrégé: J Neurosci Methods
Pays: Netherlands
ID NLM: 7905558

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 30 04 2021
revised: 30 07 2021
accepted: 25 08 2021
pubmed: 3 9 2021
medline: 7 5 2022
entrez: 2 9 2021
Statut: ppublish

Résumé

Neuronal outgrowth assays using organotypic explant cultures are commonly utilized to study neuroregenerative and -protective effects of drugs such as neurotrophins. While this approach offers higher organized tissue compared to single cell cultures and less experimental effort than in-vivo studies, quantitative evaluation of the neuronal network is often time consuming. Thus, we developed ExplantAnlayzer, a time-saving high-throughput evaluation method, yielding numerous metrics to objectively describe neuronal outgrowth. Spiral ganglion explants were cultured in 24-well plates, mechanically fixed in a collagen matrix and immunolabeled against beta-III-tubulin. The explants were imaged using a fluorescent tile-scan microscope and resulting images were stitched. The evaluation was developed as an open-source MATLAB routine and involves several image processing steps, including adaptive thresholding. The neurite network was eventually converted to a graph to track neurites from their terminals back to the explant body. We compared ExplantAnlayzer quantitatively and qualitatively to common existing methods, such as Sholl analyses and manual fiber tracing, using representative explant images. ExplantAnlayzer is able to achieve similar and as detailed results as manual tracing while decreasing manual interaction and required time dramatically. After an initial setup phase, the explant images could be batch-processed altogether. Bright bundles as well as faint fibers were reliably detected. Several metrics describing the outgrowth morphology, including total outgrowth, neurite numbers and length estimations, as well as their growth directions, were computed. ExplantAnalyzer is a time-saving and objective method for an in-depth evaluation of organotypic explant outgrowth.

Sections du résumé

BACKGROUND
Neuronal outgrowth assays using organotypic explant cultures are commonly utilized to study neuroregenerative and -protective effects of drugs such as neurotrophins. While this approach offers higher organized tissue compared to single cell cultures and less experimental effort than in-vivo studies, quantitative evaluation of the neuronal network is often time consuming. Thus, we developed ExplantAnlayzer, a time-saving high-throughput evaluation method, yielding numerous metrics to objectively describe neuronal outgrowth.
NEW METHOD
Spiral ganglion explants were cultured in 24-well plates, mechanically fixed in a collagen matrix and immunolabeled against beta-III-tubulin. The explants were imaged using a fluorescent tile-scan microscope and resulting images were stitched. The evaluation was developed as an open-source MATLAB routine and involves several image processing steps, including adaptive thresholding. The neurite network was eventually converted to a graph to track neurites from their terminals back to the explant body.
COMPARISON WITH EXISTING METHOD(S)
We compared ExplantAnlayzer quantitatively and qualitatively to common existing methods, such as Sholl analyses and manual fiber tracing, using representative explant images. ExplantAnlayzer is able to achieve similar and as detailed results as manual tracing while decreasing manual interaction and required time dramatically.
RESULTS
After an initial setup phase, the explant images could be batch-processed altogether. Bright bundles as well as faint fibers were reliably detected. Several metrics describing the outgrowth morphology, including total outgrowth, neurite numbers and length estimations, as well as their growth directions, were computed.
CONCLUSIONS
ExplantAnalyzer is a time-saving and objective method for an in-depth evaluation of organotypic explant outgrowth.

Identifiants

pubmed: 34474047
pii: S0165-0270(21)00276-4
doi: 10.1016/j.jneumeth.2021.109341
pii:
doi:

Substances chimiques

Nerve Growth Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109341

Subventions

Organisme : Austrian Science Fund FWF
ID : I 3154
Pays : Austria

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Dominik Schmidbauer (D)

Inner Ear Laboratory, Department of Otolaryngology, Medical University of Innsbruck, Innsbruck, Austria.

Stefan Fink (S)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany.

Francis Rousset (F)

The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Pascal Senn (P)

The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Clinical Neurosciences, Service of ORL & Head and Neck Surgery, University Hospital of Geneva, Geneva, Switzerland.

Marcus Müller (M)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany.

Youssef Adel (Y)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany.

Rudolf Glueckert (R)

Inner Ear Laboratory, Department of Otolaryngology, Medical University of Innsbruck, Innsbruck, Austria.

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Classifications MeSH