Temporal profile of clinical signs and histopathologic changes in an F-344 rat model of kainic acid-induced mesial temporal lobe epilepsy

Toxicologic Pathology
Alok K SharmaPaul W Snyder

Abstract

Since there is limited information in the literature, the purpose of this study was to investigate clinical signs, morphology, and temporal progression of lesions from Days 3 to 168 in a kainic acid (KA)-induced Fischer-344 (F-344) rat model of mesial temporal lobe epilepsy (MTLE). Following a single KA subcutaneous dose of 9 mg/kg to young adult male rats, 95% survived, 93% exhibited status epilepticus, and 80% eventually developed spontaneous motor seizures. Histopathology included hematoxylin and eosin (H&E), autofluorescence, Fluoro-Jade B, Timm's, ED-1/CD68, GFAP, doublecortin, and Ki-67. Neuronal degeneration occurred on Day 3 in the hippocampal CA1, CA3, and dentate hilar regions; amyg-daloid and thalamic nuclei; and frontoparietotemporal, entorhinal and piriform cortices. Degeneration severity peaked on Day 6 and decreased progressively until Day 168. Aberrant mossy fiber (MF) sprouting was present in the inner molecular layer of dentate gyrus on Days 6-168. Microliosis and astrogliosis peaked on Day 28 and generally colocalized with the distribution of neuronal degeneration. Important correlates to human MTLE included induction of spontaneous seizures, more severe neuronal damage of CA1 than CA3 (in contrast to other a...Continue Reading

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Citations

Mar 21, 2016·Experimental Neurology·Michael S HesterSteve C Danzer
Nov 5, 2013·Neuroscience and Biobehavioral Reviews·Maxime Lévesque, Massimo Avoli
Feb 27, 2010·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Germán L PerenoCarlos A Beltramino
Dec 24, 2011·Veterinary Pathology·C M BorschenskyC Herden
Nov 17, 2010·Toxicologic Pathology·P B Little, G Krinke
Dec 13, 2017·Journal of Neuroscience Research·Shaunik SharmaThimmasettappa Thippeswamy
Nov 25, 2019·Epilepsy & Behavior : E&B·Victor Rodrigues SantosOlagide Wagner de Castro

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