Differences in the toxicity of soman in various strains of mice

Clement, John G.; Hand, Brian T.; Shiloff, Janice Deborah

doi:10.1016/s0272-0590(81)80020-6

Cited by 24 publications

(5 citation statements)

References 5 publications

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“…As expected, the LD 50 in ES1−/− mice was 4-fold lower than that reported previously in wild-type C57BL/6 mice. 23 Although in ES1−/− a 4 LD 50 GD induced SE, albeit with a high survivability rate, in C57BL/6 mice an equitoxic dose induced <30 minutes of continuous seizure activity with prolonged behavioral toxicity signs and poor survival. It is notable that the C57BL/6 mouse model of temporal lobe epilepsy induced by kainic acid has severe behavioral toxicity that is not always correlated with EEG seizure activity.…”

Section: Discussionmentioning

confidence: 99%

Soman‐induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam

Marrero‐Rosado¹,

Furtado²,

Schultz³

et al. 2018

Epilepsia

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SummaryObjectiveExposure to chemical warfare nerve agents (CWNAs), such as soman (GD), can induce status epilepticus (SE) that becomes refractory to benzodiazepines when treatment is delayed, leading to increased risk of epileptogenesis, severe neuropathology, and long‐term behavioral and cognitive deficits. Rodent models, widely used to evaluate novel medical countermeasures (MCMs) against CWNA exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCMs against CWNA exposure in human casualties, it is crucial to use appropriate animal models that mirror the human condition. We present a comprehensive characterization of the seizurogenic, epileptogenic, and neuropathologic effects of GD exposure with delayed anticonvulsant treatment in the plasma carboxylesterase knockout (ES1−/−) mouse.MethodsElectroencephalography (EEG) electrode‐implanted ES1−/− and wild‐type (C57BL/6) mice were exposed to various seizure‐inducing doses of GD, treated with atropine sulfate and the oxime HI‐6 at 1 minute after exposure, and administered midazolam at 15‐30 minutes following the onset of seizure activity. The latency of acute seizure onset and spontaneous recurrent seizures (SRS) was assessed, as were changes in EEG power spectra. At 2 weeks after GD exposure, neurodegeneration and neuroinflammation were assessed.Results GD‐exposed ES1−/− mice displayed a dose‐dependent response in seizure severity. Only ES1−/− mice exposed to the highest tested dose of GD developed SE, subchronic alterations in EEG power spectra, and SRS. Degree of neuronal cell loss and neuroinflammation were dose‐dependent; no significant neuropathology was observed in C57BL/6 mice or ES1−/− mice exposed to lower GD doses.SignificanceThe US Food and Drug Administration (FDA) animal rule requires the use of relevant animal models for the advancement of MCMs against CWNAs. We present evidence that argues for the use of the ES1−/− mouse model to screen anticonvulsant, antiepileptic, and/or neuroprotective drugs against GD‐induced toxicity, as well as to identify mechanisms of GD‐induced epileptogenesis.

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Section: Discussionmentioning

confidence: 99%

Soman‐induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam

Marrero‐Rosado¹,

Furtado²,

Schultz³

et al. 2018

Epilepsia

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“…A wide variety of chemical agents have been utilized for comparing acute seizure susceptibility in different mouse strains, including traditional chemoconvulsants such as PTZ [73], picrotoxin [74], bicuculline [75], 3-mercaptopropionic acid [76], beta-carbolines [77,78], flurothyl [76], methionine sulfoximine [79], soman [80], kainic acid [81], isoniazid [60], and pilocarpine [82], as well as other drugs that are known to produce seizures clinically such as carbapenems [83], monobactams [84], anesthetic drugs [85], caffeine [77], cocaine [86], and nicotine [87]. Early studies established the relative susceptibility of DBA strains to chemoconvulsants compared to B6 strains [33], although DBA was reported to be one of the most resistant strains to nicotine-induced seizures [87].…”

Section: Interstrain Differences In the Expression Of Seizures Andmentioning

confidence: 99%

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Löscher¹,

Ferland

Ferraro

2017

Epilepsy & Behavior

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It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals’ performance in behavioral tests that often accompany acute and chronic seizure testing.

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“…Piétrain are reported to be very susceptible to stress while Landrace swine are extremely variable in type and consequently have different characteristics between countries (Bollen et al, 2000). Differences between strains for the toxic effects of OP compounds have been demonstrated in other species, such as mice (Clement et al, 1981) and it is likely that such differences also exist in swine. Gender also confers significant differences.…”

Section: Different Breedsmentioning

confidence: 99%

Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

et al. 2007

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Differences in the toxicity of soman in various strains of mice

Cited by 24 publications

References 5 publications

Soman‐induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam

Soman‐induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

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