Quantitative Neurotoxicology: An Assessment of the Neurotoxic Profile of Kainic Acid in Sprague Dawley Rats

Author:

Srivastava Anshul1ORCID,Liachenko Serguei2,Sarkar Sumit2,Paule Merle2,Negi Geeta1,Pandey Jai P.1,Hanig Joseph P.1

Affiliation:

1. US Food and Drug Administration, CDER/OPQ, Silver Spring, MD, USA

2. National Center for Toxicological Research, NCTR/DNT, Jefferson, AR, USA

Abstract

This study consisted of a qualitative and quantitative assessment of neuropathological changes in kainic acid (KA)–treated adult male rats. Rats were administered a single 10 mg/kg intraperitoneal injection of KA or the same volume of saline and sacrificed 24 or 48 hours posttreatment. Brains were collected, sectioned coronally (∼ 81 slices), and stained with amino cupric silver to reveal degenerative changes. For qualitative assessment of neural degeneration, sectioned material was evaluated by a board-certified pathologist, and the level of degeneration was graded based upon a 4-point scale. For measurement of quantitative neural degeneration in response to KA treatment, the HALO digital image analysis software tool was used. Quantitative measurements of specific regions within the brain were obtained from silver-stained tissue sections with quantitation based on stain color and optical density. This quantitative evaluation method identified degeneration primarily in the cerebral cortex, septal nuclei, amygdala, olfactory bulb, hippocampus, thalamus, and hypothalamus. The KA-produced neuronal degeneration in the cortex was primarily in the piriform, insular, rhinal, and cingulate areas. In the hippocampus, the dentate gyrus was found to be the most affected area. Our findings indicate global neurotoxicity due to KA treatment. Certain brain structures exhibited more degeneration than others, reflecting differential sensitivity or vulnerability of neurons to KA.

Funder

FDA – Center for Drug Evaluation & Research (CDER) Critical Path Program, CDER Office of Research & Testing and the National Center for Toxicological Research, Division of Neurotoxicology/FDA

Publisher

SAGE Publications

Subject

Toxicology

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