Persistent brainwave disruption and cognitive impairment induced by acute sarin surrogate sub-lethal dose exposure

Warfare neurotoxicants such as sarin, soman or VX, are organophosphorus compounds which irreversibly inhibit cholinesterase. High-dose exposure with nerve agents (NA) is known to produce seizure activity and related brain damage, while less about the effects of acute sub-lethal dose exposure. The aim this study was characterize behavioral, neuroinflammatory modifications at different time points after 4-nitrophenyl isopropyl methylphosphonate (NIMP), a sarin surrogate. In order decipher impacts exposure, we chose 4 doses NIMP each corresponding fraction median lethal (LD50). First, conducted behavioral analysis symptoms during first hour following challenge established specific scoring scale for intoxication severity. intensity signs dose-dependent proportional cholinesterase inhibition evaluated in mice brain. lowest (0.3 LD50) did not induce significant electrocorticographic (ECoG) nor changes. Animals exposed one other (0.5, 0.7 0.9 exhibited substantial changes behavior, inhibition, disruption brainwave distribution that persisted manner. To evaluate long lasting changes, ECoG recording 30 days on 0.5 LD50 NIMP. Mice both groups showed long-lasting impairment theta rhythms, lack restoration hippocampal ChE 1-month post-exposure. addition, an increase markers (IBA-1, TNF-α, NF-κB) edema were transiently observed hippocampus. Furthermore, novel object recognition test alteration short-term memory groups, post-NIMP intoxication. Our findings identified transient long-term alterations some term cognitive impairments These may further impact morphopathological