PROTECTION AGAINST NERVE AGENT-INDUCED NEUROPATHOLOGY, BUT NOT CARDIAC PATHOLOGY, IS ASSOCIATED WITH THE ANTICONVULSANT ACTION OF DRUG-TREATMENT

Brain and cardiac tissue was examined for pathological changes from ra ts that survived 24 hrs following exposure to a convulsant dose of the nerve agent soman. The animals had been treated following varying dur ations of seizure activity (2.5 - 40 min) with a number of different c ompounds that did or did not terminate the seizure. Moderate to severe neuropathology was evident in virtually all animals (98%) in which dr ug treatment did not terminate seizures. All animals that experienced up to 10 min of seizure activity before drug treatment successfully te rminated the seizure were free of neuropathology. There was an increas ing frequency in the incidence of neuropathology in animals that exper ienced 20 (10%) or 40 min (79%) of seizure activity before drug treatm ent terminated the seizure, but the degree of neuropathology in these groups was significantly less than that observed in animals where seiz ure activity was not terminated. Cardiac lesions occurred at a much hi gher frequency (88%) than neuropathological changes (57%) and were not consistently associated with the anticonvulsant effectiveness. Early treatment (less than or equal to 10 min) with anticholinergic drugs, h owever, was associated with protection from cardiac damage. The result s strongly support the hypothesis that nerve agent-induced brain damag e is linked to epileptiform activity. The minimal amount of seizure ac tivity necessary for irreversible neural damage to become evident unde r these conditions is similar to 20 min, and the process accelerates g reatly after this minimal time has elapsed. Successful termination of seizure activity, regardless of the type of drug used, protected eithe r totally or relatively against brain damage depending upon how long t he seizure had progressed. The mechanisms responsible for cardiac lesi on formation occur more rapidly and may have a cholinergic component. (C) 1995 Intox Press, Inc.