Cerebrospinal Fluid Analysis in Toxicological Neuropathology

Vernau, William; Vernau, Karen M.; Bolon, Brad

doi:10.1002/9780470939956.ch19

Cited by 2 publications

(2 citation statements)

References 75 publications

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“…Soluble biomarkers in fluid samples (e.g., blood, CSF, urine) obtained by minimally or non-invasive methods are an area of intense interest as a means of monitoring neural injury. 163,164 Currently, neurofilament light chain (NfL) and less commonly neurofilament heavy chain (NfH) proteins are the most common biomarkers of neural injury evaluated in nonclinical species and human patients, including neurodegenerative diseases, nervous system infections, and nervous system neoplasia as well as neurotoxic conditions. [165][166][167] For example, serum neurofilament concentrations are increased in animal models and cancer patients with chemotherapy-induced peripheral neuropathy (CIPN).…”

Section: Correlation Between Functional and Structural Findings In Se...mentioning

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: Correlation Between Functional and Structural Findings In Se...mentioning

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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“…She discussed the need for noninvasive, fluid-based biomarkers that can help predict neurotoxicity or aid the understanding of neurological disease in nonclinical species and humans. Such biomarkers of neurological damage are uncommon for both the CNS and PNS (Vernau, Vernau, and Bolon 2011;Apostolidis et al 2017), but many scientists are collaborating to develop and test biomarkers for neurotoxicity applications. Recent progress includes the Health Education Systems Incorporated Subcommittee on Translational Biomarkers of Neurotoxicity (Roberts et al 2015), the European Union's Innovative Medicines Initiative Translational Safety Biomarker Pipeline (IMI-2 TransBioLine) effort to identify and validate new biomarkers of CNS injury (http://ec.europa.eu/research/participants/portal/desktop/en/opportunities/ h2020/topics/imi2-2017-13-11.html), and the recent U.S. Food and Drug Administration authorization of the first blood test to aid in the evaluation of traumatic brain injury (TBI) in humans (Takala et al 2016).…”

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confidence: 99%

Toxicologic Pathology of the Peripheral Nervous System (PNS): Overview, Challenges, and Current Practices

et al. 2018

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Peripheral nervous system (PNS) toxicity is a frequent adverse effect encountered in patients treated with certain therapeutics (e.g., antiretroviral drugs, cancer chemotherapeutics), in occupational workers exposed to industrial chemicals (e.g., solvents), or during accidental exposures to household chemicals and/or environmental agents (e.g., pesticides). However, the literature and expertise needed for the effective design, conduct, analysis, and reporting of safety studies to identify and define PNS toxicity are hard to find. This half-day course familiarized participants with basic PNS biology; causes and mechanisms of PNS pathology; classic methods and current best practice recommendations for PNS sampling, preparation, and evaluation; and examples of commonly observed lesions and artifacts. Three concluding case presentations synthesized information from the prior technical lectures by presenting real-world examples of lesions caused by drugs and chemicals to demonstrate how PNS toxicity may be addressed in evaluating product safety during nonclinical studies. Topics emphasized comparative and correlative data among animal species used in toxicity studies and clinical evaluation in humans in order to facilitate the translation of animal data into human risk assessment with respect to PNS toxicologic pathology.

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Cerebrospinal Fluid Analysis in Toxicological Neuropathology

Cited by 2 publications

References 75 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

Toxicologic Pathology of the Peripheral Nervous System (PNS): Overview, Challenges, and Current Practices

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