TY  - JOUR
PY  - 2020//
TI  - Characterization of organophosphate-induced brain injuries in a convulsive mouse model of diisopropylfluorophosphate exposure
JO  - Epilepsia
A1  - Enderlin, Julie
A1  - Igert, Alexandre
A1  - Auvin, Stéphane
A1  - Nachon, Florian
A1  - Dal Bo, Grégory
A1  - Dupuis, Nina
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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.<br><br>© 2020 International League Against Epilepsy.<p />  <p>Language: en</p>
LA  - en
SN  - 0013-9580
UR  - http://dx.doi.org/10.1111/epi.16516
ID  - ref1
ER  -