Effects of atropine sulphate on seizure activity and brain damage producedby soman in guinea-pigs: ECoG correlates of neuropathology

The present study describes the effects of pyridostigmine (PYR; 0.2 mg/kg) and atropine sulphate (AS; 5 mg/kg) on guinea-pigs intoxicated by a high do se (2xLD50) of the organophosphate compound, oman, an irreversible inhibito r of acetylcholinesterase. The medication was shown to counteract the acute respiratory distress and lethality normally produced by the intoxication. Moreover, due to the central activity of AS, soman-induced electrocorticogr aphic (ECoG) seizure activity was either totally prevented, or reduced in d uration and overall intensity. In addition, as established in the 24-hr sur vivors, seizure-related neuropathology was either prevented, or reduced in topographical extent and severity. An attempt to correlate our electrograph ic and morphological findings gives evidence that (a), the occurrence of se izure activity is the primary factor necessary for the development of acute neuropathology; (b) the duration of ECoG seizures is a secondary factor, o n which the topographical distribution of brain damage finally depends; (c) , the minimal duration of seizures necessary to produce 24 hr-damage in the most sensitive areas (e.g. the amygdala) is less than 70 min; (d), the ove rall intensity/power of epileptifbrm discharges is a tertiary factor which influences the severity of damage; (e), in addition, ECoG power spectral an alysis suggested that an acute increase of relative power in the lower (del ta) frequency band might be a real-time external marker of the starting cer ebral lesions and is thus predictive for their future installation. All the se data confirm the tight relationships which exist between seizure activit y and neuropathology in soman poisoning, and suggest that refined, standard ized analysis of electrographic parameters drawn from ECoG tracings and pow er spectrum might serve as a useful tool to predict the presence, localizat ion, and severity of soman-induced brain damage. (C) 2000 Intox Press, Inc.