NDLI: Susceptibility to Soman Toxicity and Efficacy of LY293558 Against Soman-Induced Seizures and Neuropathology in 10-Month-Old Male Rats

Content Provider	Springer Nature Link
Author	Apland, James P. Aroniadou Anderjaska, Vassiliki Figueiredo, Taiza H. Prager, Eric M. Olsen, Cara H. Braga, Maria F. M.
Copyright Year	2017
Abstract	Acute nerve agent exposure causes prolonged status epilepticus (SE), leading to death or long-term brain damage. We have previously demonstrated that LY293558, an AMPA/GluK1 kainate receptor antagonist, terminates SE induced by the nerve agent soman and protects from long-term brain damage, in immature rats and young-adult rats, even if administered with a relatively long latency from the time of exposure. However, susceptibility to the lethal consequences of SE increases with age, and mortality by SE induced by soman is substantially greater in older animals. Therefore, in the present study, we compared the susceptibility to soman toxicity of 10-month-old male rats with that of young-adult male rats (42 to 50 days old) and examined the protective efficacy of LY293558 in the older group. A lower percentage of the 10-month-old rats developed SE after injection of 1.2 × LD$_{50}$ soman, compared to the young adults, the latency to seizure onset was longer in the older rats, and seizure intensity did not differ between the two age groups. However, mortality rate in the older rats who developed SE was higher than in the young adults. Acetylcholinesterase activity in the amygdala, hippocampus, and piriform cortex did not differ between the two age groups. Administration of LY293558 at 20 or 60 min post-exposure suppressed SE, increased 24-h survival rate, decreased the long-term risk of death, reduced neuronal degeneration in the amygdala, hippocampus, piriform, and entorhinal cortices, and facilitated recovery from body weight loss. Thus, LY293558 is an effective countermeasure against soman toxicity also in older animals.
Starting Page	694
Ending Page	706
Page Count	13
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	32
Issue Number	4
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2017-08-03
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Nerve agents Status epilepticus Seizures AMPA receptors GluK1-kainate receptors Aging Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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