Characterization of organophosphate-induced brain injuries in a convulsive mouse model of diisopropylfluorophosphate exposure.
Julie EnderlinAlexandre IgertStėphane AuvinFlorian NachonGregory Dal-BoNina DupuisPublished in: Epilepsia (2020)
Organophosphate (OP) compounds constitute a class of highly toxic molecules, characterized by irreversible cholinesterase (ChE) inhibition. Being either pesticides or chemical warfare agents, they present a major health issue in some countries, as well as a terrorist or military threat. Prompted by the need for suitable animal models to test novel medical countermeasures, we developed a new convulsive mouse model of OP poisoning using diisopropylfluorophosphate (DFP). Using electrocorticography (ECoG), we analyzed seizure and status epilepticus (SE) occurrences, as well as relative power of ECoG frequency band modifications after DFP injection in male Swiss mice. Next, we investigated DFP effect on ChE inhibition. Histological changes on neuronal activity and neuronal damage were examined by c-Fos immunolabeling and Fluoro-Jade C staining. We showed that mice exposed to DFP presented electrocorticographic seizures that rapidly progressed to SE within 20 minutes. Lasting >8 hours, DFP-induced SE was associated with major power spectrum modifications in seizing DFP animals compared to control animals. Seizures and SE development were concomitant with profound ChE inhibition and induced massive neuronal degeneration. Presenting all hallmarks of convulsive OP poisoning, we showed that our mouse model is valuable for studying pathophysiological mechanisms and preclinical testing of newly available therapeutic molecules.
Keyphrases
- mouse model
- high glucose
- diabetic rats
- healthcare
- public health
- oxidative stress
- drug induced
- cerebral ischemia
- type diabetes
- high fat diet induced
- computed tomography
- insulin resistance
- autism spectrum disorder
- climate change
- positron emission tomography
- stem cells
- brain injury
- endothelial cells
- functional connectivity
- case report
- atomic force microscopy
- high speed
- ultrasound guided