Single whole-body exposure to sarin vapor in rats: Long-term neuronal and behavioral deficits

Efficacy of the GluK1/AMPA Receptor Antagonist LY293558 against Seizures and Neuropathology in a Soman-Exposure Model without Pretreatment and its Pharmacokinetics after Intramuscular Administration

“…seizures are not controlled effectively, the seizure-induced brain damage can have long-term consequences on cognitive and emotional functions (McDonough et al, 1986;Brown and Brix, 1998;Myhrer et al, 2005;Grauer et al, 2008).…”

“…As the primary action of nerve agents is the inhibition of acetylcholinesterase (AChE), the main causes of acute death after nerve agent exposure are cardiorespiratory depression and intense seizure activity [status epilepticus (SE)], which are due to elevated acetylcholine levels in the peripheral and central nervous system (for reviews see Bajgar, 2005;Collombet, 2011). If death is prevented but SE is not controlled in a timely manner, the ensuing brain damage from the intense seizures can produce long-term cognitive and other behavioral deficits (McDonough et al, 1986;Brown and Brix, 1998;Myhrer et al, 2005;Grauer et al, 2008). Research aimed at developing effective medical countermeasures to terminate seizure activity and prevent brain damage by nerve agent exposure has traditionally used models in which the animal is pretreated with an oxime or pyridostigmine.…”

Neuropathologic Effects of Chemical Warfare Agents

“…A number of studies describe the long-term effects of nerve agent exposure on the cerebrum (Lemercier et al, 1983;Kadar et al, 1992;McDonough et al, 1998;Collombet et al, 2005aCollombet et al, , 2006Grauer et al, 2008). Inflammatory changes are pronounced and may occur in two phases-namely, an initial response to cholinergic cell death, as well as a second, delayed inflammatory process that begins approximately 1 month after exposure and persists for at least several months (Grauer et al, 2008).…”

“…Inflammatory changes are pronounced and may occur in two phases-namely, an initial response to cholinergic cell death, as well as a second, delayed inflammatory process that begins approximately 1 month after exposure and persists for at least several months (Grauer et al, 2008). Morphologically, reactive changes that may be seen with many etiologies of brain tissue injury may be observed if survival is sufficiently prolonged after exposure.…”

Long‐Term Neurotoxicological Effects of Anticholinesterases after either Acute or Chronic Exposure

“…Kassa et al (2001) also showed some alterations on motor activity and stereotyped behavior in rats exposed three months earlier by inhalation to sarin that caused cholinergic syndrome although without convulsions. Grauer et al (2008) exposed rats for 10 minutes to a single high-level air concentration (whole body) of sarin. There was high mortality (about 35%) and among surviving rats, a group (75%) showed clear signs of toxicity, including convulsions, and another group (25%) did not show overt signs of toxicity.…”