Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

“…The data reported so far show that midazolam can protect against nerve agent-induced brain damage in adult or young-adult rats, if it is administered at the time of exposure (Chapman et al, 2015), at the onset of seizures (RamaRao et al, 2014), or after 5 min of seizure activity (Gilat et al, 2005); however, if it is given 1 h after exposure, it does not prevent histological damage, despite its antiseizure efficacy and beneficial effects on behavioral performance and inflammatory responses (Chapman et al, 2015). More studies are needed to understand the neuroprotective efficacy of midazolam when administered at different time points after nerve agent exposure, and direct comparisons must be made with LY293558 under the same experimental conditions for two drugs.…”

The GluK1 (GluR5) Kainate/α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Antagonist LY293558 Reduces Soman-Induced Seizures and Neuropathology

“…Accordingly, muscarinic receptor antagonists are effective against nerve agent-induced SE only if administered early after the onset of seizures (Lallement et al, 1998). Benzodiazepines are considered to be the first line of defense against nerve agent-induced SE, but the effectiveness of benzodiazepines is transient (seizures recur), and it is reduced or lost if administration is delayed beyond 30 to 40 min after nerve agent exposure (Lallement et al, 1998;Gilat et al, 2005;McDonough et al, 2010). …”

“…For this reason, muscarinic receptor antagonists are effective only when administered at a short latency after exposure (Lallement et al, 1998). Benzodiazepines can stop nerve agent-induced seizures, at least temporarily; however, these drugs also start losing their efficacy if administered with a latency longer than 30 to 40 min after the initiation of seizures (Lallement et al, 1998;Gilat et al, 2005;McDonough et al, 2010). This may be caused, in part, by internalization of benzodiazepine-sensitive GABA A receptors, which is known to occur in some brain regions during prolonged seizures (Naylor et al, 2005;Goodkin et al, 2008).…”

A new post-intoxication treatment of paraoxon and parathion poisonings using an evolved PON1 variant and recombinant GOT1

“…Refs. [52,53]), biochemical assays can examine brain AChE activity or damage related protein markers such as translocator protein (TSPO [53]), magnetic resonance imaging (MRI) may be used to detect enlargement of ventricle size in the brain (e.g. Ref.…”