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Published on: August 15, 2017
Chronic Epilepsy and Mossy Fiber Sprouting Following Organophosphate-Induced Status Epilepticus in Rats
Robert E Blair1, Elisa Hawkins1, Lauren R Pinchbeck1
1Departments of Neurology (R.E.B., E.H., R.J.D., L.S.D.) and Pharmacology and Toxicology (R.J.D., L.S.D.) School of Medicine, and Department of Biology, College of Humanities & Sciences (L.R.P.), Virginia Commonwealth University, Richmond, Virginia.
Organophosphate (OP) exposure causes status epilepticus (SE), leading to hippocampal damage and chronic seizures in over 60% of survivors. This OP-induced SE model reveals key epilepsy hallmarks for therapeutic development.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphate (OP) compounds, including pesticides and nerve agents, are highly toxic.
- OP exposure inhibits acetylcholinesterase, leading to cholinergic overstimulation, status epilepticus (SE), and potential lethality.
- Survival from OP-induced SE is linked to mood, memory deficits, and spontaneous recurrent seizures (SRS).
Purpose of the Study:
- To assess hippocampal pathology and chronic SRS in rats following OP-induced SE.
- To investigate the long-term consequences of OP exposure on brain function and epilepsy development.
Main Methods:
- Male Sprague-Dawley rats received OP agents (paraoxon, diisopropyl fluorophosphate, or sarin) to induce SE, followed by atropine and 2-PAM.
- SE was controlled with midazolam at 1-hour post-onset.
- Chronic SRS were evaluated ~6 months post-SE using video and electroencephalography.
- Histopathology included H&E staining for neuronal loss and Timm staining for mossy fiber sprouting (MFS).
Main Results:
- Over 60% of rats surviving OP-induced SE developed chronic SRS.
- H&E staining showed significant hippocampal neuronal loss.
- Timm staining revealed extensive MFS in the dentate gyrus's inner molecular layer.
- Findings indicate OP-induced SE causes hallmarks of chronic epilepsy.
Conclusions:
- OP-induced SE in rats leads to hippocampal pathology, including neuronal loss and mossy fiber sprouting.
- This model is associated with the development of chronic spontaneous recurrent seizures (SRS), mimicking epilepsy.
- This OP-induced SE model serves as a resource for studying OP toxicities and screening therapeutics.
