Sarin, a potent
organophosphate cholinesterase inhibitor, induces an array of toxic effects including convulsions. Many antidotal treatments contain
anticonvulsants to block seizure activity and the ensuing brain damage.
Magnesium sulfate (MGS) is used to suppress eclamptic
seizures in pregnant women with
hypertension and was shown to block
kainate-induced convulsions.
Magnesium sulfate was evaluated herein as an
anticonvulsant against
sarin poisoning and its efficacy was compared with the potent
anticonvulsants midazolam (MDZ) and
caramiphen (CRM). Rats were exposed to a
convulsant dose of
sarin (96 μg/kg, im) and 1 min later treated with the
oxime TMB4 and
atropine to increase survival. Five minutes after initiation of convulsions, MGS, CRM, or MDZ were administered. Attenuation of
tonic-clonic convulsions was observed following all these treatments. However, radio-telemetric electro-corticography (ECoG) monitoring demonstrated sustained seizure activity in MGS-injected animals while this activity was completely blocked by MDZ and CRM. This disrupted brain activity was associated with marked increase in brain translocator
protein levels, a marker for brain damage, measured 1 week following exposure. Additionally, histopathological analyses of MGS-treated group showed typical
sarin-induced
brain injury excluding the hippocampus that was partially protected. Our results clearly show that MGS demonstrated misleading features as an
anticonvulsant against
sarin-induced
seizures. This stems from the dissociation observed between overt convulsions and seizure activity. Thus, the presence or absence of motor convulsions may be an unreliable
indicator in the assessment of clinical status and in directing adequate antidotal treatments following exposure to
nerve agents in battle field or terror attacks.