Toxicological Neuropathology of the Ear

Forge, Andrew; Taylor, Ruth; Bolon, Brad

doi:10.1002/9780470939956.ch25

Cited by 3 publications

(3 citation statements)

References 151 publications

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“…3,7 In contrast, the SG are sampled only in dedicated ototoxicity studies as their location encased within thick bone of the skull requires special tissue processing methods unsuitable for conventional nonclinical toxicity studies. 37,38 In general, evaluation of DRG (± TG) but not SG is an acceptable approach for screening sensory ganglia for neurotoxicity in nonclinical studies.…”

Section: Biology Fundamentals For Gangliamentioning

confidence: 99%

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

Bennet,

Pardo,

Assaf

et al. 2023

Toxicol Pathol

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Certain biopharmaceutical products consistently affect dorsal root ganglia, trigeminal ganglia, and/or autonomic ganglia. Product classes targeting ganglia include antineoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, and anti-nerve growth factor agents. This article outlines “points to consider” for sample collection, processing, evaluation, interpretation, and reporting of ganglion findings; these points are consistent with published best practices for peripheral nervous system evaluation in nonclinical toxicity studies. Ganglion findings often occur as a combination of neuronal injury (e.g., degeneration, necrosis, and/or loss) and/or glial effects (e.g., increased satellite glial cell cellularity) with leukocyte accumulation (e.g., mononuclear cell infiltration or inflammation). Nerve fiber degeneration and/or glial reactions may be seen in nerves, dorsal spinal nerve roots, spinal cord, and occasionally brainstem. Interpretation of test article (TA)-associated effects may be confounded by incidental background changes or experimental procedure-related changes and limited historical control data. Reports should describe findings at these sites, any TA relationship, and the criteria used for assigning severity grades. Contextualizing adversity of ganglia findings can require a weight-of-evidence approach because morphologic changes of variable severity occur in ganglia but often are not accompanied by observable overt in-life functional alterations detectable by conventional behavioral and neurological testing techniques.

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Section: Biology Fundamentals For Gangliamentioning

confidence: 99%

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

Bennet,

Pardo,

Assaf

et al. 2023

Toxicol Pathol

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“…The dendrites of SG sensory neurons synapse with auditory hair cells in the spiral organ (of Corti) located at the center of the cochlea, after which the axons come together to form the cochlear nerve (CN VIII). 73 Neurons in the SG exhibit two conformations. 39 Approximately, 95% of SG neurons are bipolar (type I) cells with separate myelinated neurites (one axon and one dendrite) originating from two poles of the cell body; each type I SG neuron innervates a single inner hair cell (ie, the sensory receptor cells that transduce airborne vibrations into acoustic signals).…”

Section: Comparative Neurobiology Of Gangliamentioning

confidence: 99%

“…99,123 In contrast, the SG generally are collected only in special ototoxicity studies since their location buried within thick bone of the skull requires special tissue processing methods unsuitable for routine nonclinical studies. 73,199 In general, evaluation of DRG (± TG) but not SG is a suitable approach for screening sensory ganglia for neurotoxicity in routine nonclinical studies.…”

Section: Comparative Neurobiology Of Gangliamentioning

confidence: 99%

Scientific and Regulatory Policy Committee Technical Review: Biology and Pathology of Ganglia in Animal Species Used for Nonclinical Safety Testing

Bennet,

Pardo,

Assaf

et al. 2023

Toxicol Pathol

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Dorsal root ganglia (DRG), trigeminal ganglia (TG), other sensory ganglia, and autonomic ganglia may be injured by some test article classes, including anti-neoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, nerve growth factor inhibitors, and aminoglycoside antibiotics. This article reviews ganglion anatomy, cytology, and pathology (emphasizing sensory ganglia) among common nonclinical species used in assessing product safety for such test articles (TAs). Principal histopathologic findings associated with sensory ganglion injury include neuron degeneration, necrosis, and/or loss; increased satellite glial cell and/or Schwann cell numbers; and leukocyte infiltration and/or inflammation. Secondary nerve fiber degeneration and/or glial reactions may occur in nerves, dorsal spinal nerve roots, spinal cord (dorsal and occasionally lateral funiculi), and sometimes the brainstem. Ganglion findings related to TA administration may result from TA exposure and/or trauma related to direct TA delivery into the central nervous system or ganglia. In some cases, TA-related effects may need to be differentiated from a spectrum of artifactual and/or spontaneous background changes.

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Special senses

Scudamore¹

2013

A Practical Guide to the Histology of the Mouse

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Toxicological Neuropathology of the Ear

Cited by 3 publications

References 151 publications

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

Scientific and Regulatory Policy Committee Technical Review: Biology and Pathology of Ganglia in Animal Species Used for Nonclinical Safety Testing

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