Persistent neuropathology and behavioral deficits in a mouse model of status epilepticus induced by acute intoxication with diisopropylfluorophosphate Article Swipe
Jonas J. Calsbeek
,
Eduardo A. González
,
Donald A. Bruun
,
Michelle Guignet
,
Nycole A. Copping
,
Mallory E. Dawson
,
Alexandria J. Yu
,
Jeremy A. MacMahon
,
Naomi Saito
,
Danielle Harvey
,
Jill L. Silverman
,
Pamela J. Lein
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.neuro.2021.09.001
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.neuro.2021.09.001
Organophosphate (OP) nerve agents and pesticides are a class of neurotoxic compounds that can cause status epilepticus (SE), and death following acute high-dose exposures. While the standard of care for acute OP intoxication (atropine, oxime, and high-dose benzodiazepine) can prevent mortality, survivors of OP poisoning often experience long-term brain damage and cognitive deficits. Preclinical studies of acute OP intoxication have primarily used rat models to identify candidate medical countermeasures. However, the mouse offers the advantage of readily available knockout strains for mechanistic studies of acute and chronic consequences of OP-induced SE. Therefore, the main objective of this study was to determine whether a mouse model of acute diisopropylfluorophosphate (DFP) intoxication would produce acute and chronic neurotoxicity similar to that observed in rat models and humans following acute OP intoxication. Adult male C57BL/6J mice injected with DFP (9.5 mg/kg, s.c.) followed 1 min later with atropine sulfate (0.1 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.) developed behavioral and electrographic signs of SE within minutes that continued for at least 4 h. Acetylcholinesterase inhibition persisted for at least 3 d in the blood and 14 d in the brain of DFP mice relative to vehicle (VEH) controls. Immunohistochemical analyses revealed significant neurodegeneration and neuroinflammation in multiple brain regions at 1, 7, and 28 d post-exposure in the brains of DFP mice relative to VEH controls. Deficits in locomotor and home-cage behavior were observed in DFP mice at 28 d post-exposure. These findings demonstrate that this mouse model replicates many of the outcomes observed in rats and humans acutely intoxicated with OPs, suggesting the feasibility of using this model for mechanistic studies and therapeutic screening.
Related Topics
Concepts
Status epilepticus
Neuropathology
Pralidoxime
Medicine
Organophosphate poisoning
Atropine
Neuroinflammation
Neurotoxicity
Pharmacology
Anesthesia
Nerve agent
Diazepam
Acetylcholinesterase
Organophosphate
Toxicity
Internal medicine
Epilepsy
Inflammation
Chemistry
Biology
Disease
Pesticide
Biochemistry
Psychiatry
Agronomy
Enzyme
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.neuro.2021.09.001
- OA Status
- hybrid
- Cited By
- 12
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3200211469
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3200211469Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.neuro.2021.09.001Digital Object Identifier
- Title
-
Persistent neuropathology and behavioral deficits in a mouse model of status epilepticus induced by acute intoxication with diisopropylfluorophosphateWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-09-09Full publication date if available
- Authors
-
Jonas J. Calsbeek, Eduardo A. González, Donald A. Bruun, Michelle Guignet, Nycole A. Copping, Mallory E. Dawson, Alexandria J. Yu, Jeremy A. MacMahon, Naomi Saito, Danielle Harvey, Jill L. Silverman, Pamela J. LeinList of authors in order
- Landing page
-
https://doi.org/10.1016/j.neuro.2021.09.001Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1016/j.neuro.2021.09.001Direct OA link when available
- Concepts
-
Status epilepticus, Neuropathology, Pralidoxime, Medicine, Organophosphate poisoning, Atropine, Neuroinflammation, Neurotoxicity, Pharmacology, Anesthesia, Nerve agent, Diazepam, Acetylcholinesterase, Organophosphate, Toxicity, Internal medicine, Epilepsy, Inflammation, Chemistry, Biology, Disease, Pesticide, Biochemistry, Psychiatry, Agronomy, EnzymeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
12Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 5, 2023: 5, 2022: 2Per-year citation counts (last 5 years)
- References (count)
-
68Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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