Neurochemical Mechanisms in Soman-induced Seizures

Nerve agent exposure elicits site-specific changes in protein phosphorylation in mouse brain

“…These data are consistent with reports that nerve agents induce a sequential activation of distinct neurochemical systems in the brain resulting in a delayed recruitment of glutamatergic neurons (Shih & McDonough; 1997; Shih et al, 2003). A rapid reduction was seen in the level of NR1 phosphorylated at the S897 residue in mouse striatum at the earliest time point monitored after DFP exposure (15 min in female C57BL/6 mice and 30 min in male FVB mice).…”

Trafficking of the muscarinic m2 autoreceptor in cholinergic basalocortical neurons in vivo: Differential regulation of plasma membrane receptor availability and intraneuronal localization in acetylcholinesterase‐deficient and ‐inhibited mice

“…The m2R was expressed in 25% of them and was considered there as a presynaptic autoreceptor. Taken together, our data give anatomic basis for a regulation through m2R of acetylcholine but also of GABA and glutamate release in cortex, in agreement with biochemical data (Shih and McDonough, 1997; Zhang et al, 2002).…”

Anticonvulsants for soman-induced seizure activity

“…The data show that diazepam can block the onset of soman-induced seizures when given as a pretreatment, and this would be consistent with other data showing it can suppress ongoing seizure activity and with its known mechanism of action on the GABA system [ 1,26,28,31,48]. This also would agree with the proposed model of nerve agent seizures in that seizure initiation is due to an overwhelming of normal inhibitory activity (GABA-mediated) by excessive neuronal excitation due to cholinergic overstimulation [30,31,33,45,46]. The data with atropine sulfate also show that anticonvulsant dose levels of this drug when given as a pretreatment agree more closely with other data obtained using EEG monitoring of seizures [31 ] than using observation of motor convulsions [8].…”

“…However, from the results of this study and the basic studies reported above, it is apparent that diazepam may have limited effectiveness by itself when treatment is delayed for 40 min. These data reinforce the contention that seizures induced by nerve agents are unlike other epileptic conditions and that the seizures are initiated and maintained by a specific series of neurochemical perturbations brought on by the central action of these agents [45,46]. 40 min after onset of soman-induced seizures was effective in terminating epileptiform activity in 66% of the rats tested [31 ].…”