Subsite Awareness in Neuropathology Evaluation of National Toxicology Program (NTP) Studies

Rao, Deepa B.; Little, P B; Sills, Robert C.

doi:10.1177/0192623313501893

Cited by 36 publications

(13 citation statements)

References 121 publications

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“…These neuroanatomical areas represent important sites which comprise the population of neurons and glia cells vulnerable for neurodegerative conditions and or ageing processes in vertebrate animals. These also correspond to the neuroanatomical parts of the brain outline for neurologic studies in large animals (6,14,38,45). Changes observed in this study were consistent with changes reported by Gavier-Waden et al (15) who reported them as incidental findings in older cattle.…”

Section: Discussionsupporting

confidence: 91%

Age, and non-age-related cytoarchitectural changes in the brain of some Nigerian cattle

Shawulu¹,

Hambolu²,

Olopade3³

et al. 2023

BJVP

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Brain is the most vulnerable organ in the body to the ageing processes which operates at variable levels between organs and species. In this study we examine brains histopathologically for architectural changes in four Nigerian cattle breeds. Brains from 246 cattle (Bunaji=80, Muturu=78, Rahaji=62 and Sokoto Gudali=26), aged 1–≥12years were examined at 8 different neuroanatomical locations. All the cattle used were obtained from Abattoir in Ibadan, Nigeria. They were examined at ante-mortem and those without clinical signs suggestive of neurological disease were sampled. Major changes observed were intracellular accumulation of substances (61.4%), neuronal and or axonal degenerations and loss (51.6%), perivascular cuffing (50.0%), extracellular accumulation of substances (29.7%), hypercellularity (19.1%) and spongy state (0.4%), malacia (0.0%), demyelination (0.0%) in 233 cattle. Intraneuronal vacuolations (35%), lipofuscin accumulation (42%), axonal spheroids (50%), inflammatory changes (50%), and brain sand (22%). Although perivascular cuffing was high, there was low incidence of lymphocytic infiltration in the pineal gland in both sexes. Intracellular accumulation of substances, neuronal and or axonal degenerations and loss, and extracellular accumulation of substances display levels of significant changes with age (p<0.0001). Changes starts at the age of 2 years in life in these breeds of cattle due probably to the adverse stress exerted by the tropical climate. The description of histological findings in the brain of symptomless cattle in the present study provides a useful background for diagnostic bovine neuropathology in the tropics.

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Section: Discussionsupporting

confidence: 91%

Age, and non-age-related cytoarchitectural changes in the brain of some Nigerian cattle

Shawulu¹,

Hambolu²,

Olopade3³

et al. 2023

BJVP

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“…The head of the animal was skinned, decapitated and immersion fixed for 24 hours in 10% NBF before brain removal. The brains were fixed for an additional five days before trimming into nine 5-mm coronal slices [ 51 , 52 ] using a brain-trimming matrix (Zivic). Tissues were processed in an automated Tissue-Tek VIP processor and paraffin-embedded with a Tissue-Tek TEC embedding station (Sakura Finetek USA, Torrance, CA).…”

Section: Methodsmentioning

confidence: 99%

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

et al. 2015

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BackgroundAcute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1- describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2- determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.MethodsNaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg IV) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7.ResultsSixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.ConclusionIn conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

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“…The sections were slide mounted and then stained with hematoxylin and eosin (H&E) or luxol fast blue counterstaineds with cresyl violet (LFB/CV). Specific neuroanatomic landmarks were identified and examined via light microscopy according to Rao et al 1,9 and Paxinos and Wason. 10 Paxinos and Watson's atlas was used in lieu of the Nomina Anatomica Veterinaria because the use of this atlas is integral to the neuroanatomic locations and calculations used by stereology and MRM.…”

Section: Methods: Neuropathologymentioning

confidence: 99%

Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats

Sills

Johnson

et al. 2020

Toxicol Pathol

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It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.

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Subsite Awareness in Neuropathology Evaluation of National Toxicology Program (NTP) Studies

Cited by 36 publications

References 121 publications

Age, and non-age-related cytoarchitectural changes in the brain of some Nigerian cattle

Age, and non-age-related cytoarchitectural changes in the brain of some Nigerian cattle

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats

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