Technical Guide for Nervous System Sampling of the Cynomolgus Monkey for General Toxicity Studies

Abstract

For general toxicity studies, a technique was designed to consistently sample the most important neuroanatomic regions of the brain, spinal cord, and peripheral nerve of cynomolgus monkeys using a limited number of blocks and slides. Using the most rostral portion of the pons as a landmark, the entire fixed brain was cut dorsoventrally into cross-sectional slabs 4 mm in thickness. For microscopic evaluation, six blocks of the brain at the levels of the frontal pole, anterior commissure, rostral thalamus, caudal thalamus, middle cerebellum with brainstem, and occipital lobe were trimmed to fit in standard tissue cassettes. Cross- and oblique sections of the spinal cord including the dorsal root ganglion and dorsal and ventral nerve roots were obtained at the levels of C1-C4, T10-T12, and L1-L4. Cross- and longitudinal sections of the sciatic nerve were also obtained. This technique offers a consistent and reliable method to routinely sample most of the important regions of the central and peripheral nervous system of monkeys using ten blocks. This method is readily adaptable to other species of nonhuman primates, dogs, and minipigs and can be quickly learned by the technicians performing the trimming procedures.

Performance Evaluation of a High-Resolution Nonhuman Primate PET/CT System

“…Accurate quantification of neuroreceptors and brain imaging targets in NHPs requires high resolution, considering the relatively small size of the NHP brain. The estimated brain volume for a cynomolgus or rhesus monkey is 70-90 cm 3 , approximately 15 times smaller than the volume of the human brain (12,13). Therefore, the development of a dedicated PET system for brain imaging in NHPs is an important component of the translational chain from small animals to humans.…”

Oral Pretreatment with Galantamine Effectively Mitigates the Acute Toxicity of a Supralethal Dose of Soman in Cynomolgus Monkeys Posttreated with Conventional Antidotes

“…Using a Leica CM 3000 cryostat (Leica Biosystems, Buffalo Grove, IL), frozen brains were cut, according to the technique described by Pardo et al (2012), in 30-µm thick sections (for Fluoro Jade-B -FJBstaining) or 50-µm sections (for NeuN immunohistochemistry) that were anatomically matched and contained the hippocampus. The sections were, then, transferred to wells containing PBS.…”

Toxicologic Pathology Analysis for Translational Neuroscience

“…13,15,16 Structural/functional correlations have also been demarcated for spinal cord. 15 Pathologists who frequently participate in neuropathology analysis for nonclinical studies should also be conversant with the many other resources that are available for data translation across species. 18,30,31 In the future, lesion identification by routine histopathologic evaluation is likely to be supplemented by noninvasive or minimally invasive methods.…”

“…Basic considerations include the study purpose (eg, general screen vs dedicated neurotoxicity analysis), processing conditions (eg, tissue fixation by immersion for general toxicity studies vs perfusion for dedicated neurotoxicity studies), embedding medium (eg, paraffin vs plastic), and nervous system sampling strategy. [12][13][14][15][16][17] In some instances, these details reflect the preferences of the sponsoring institution and/or the scientific team. In other cases, study parameters are dictated by regulatory guidelines.…”