Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound.

The effect of soman, a powerful organophosphorus (OP) cholinesterase inhibitor, was investigated in the central nervous system (CNS) of Wistar rats by neurohistology, histochemical mapping of acetylcholinesterase (AChE), and biochemical determination of cholinesterase (ChE) activity. Rats were poisoned by one lethal or sublethal subcutaneous (s.c.) injection or by several less strong weekly doses. When the acute cholinergic action of the OP led to severe respiratory failure and to repeated or prolonged convulsions, the surviving rats exhibited neuronal changes similar to those of hypoxic encephalopathy. In one case chronic intoxication gave rise to these symptoms and lesions after the fourth injection. The histochemical data showed that lesioned gray structures were generally poor in AChE. The enzymatic inhibition was quick and strong, but differed from one structure to another. ChE recovery was rapid until about 96 h after poisoning, the time course depending on the structure, but was incomplete even after 8 days. An attempt to correlate the initial level of ChE inhibition with the severity of the symptoms was not very conclusive. Our data suggest that the encephalopathy comes at least in part from complex hypoxic factors produced by the cholinergic crisis. The sequelae of slight hypoxic encephalopathy could account for some nervous long-term effects in men acutely poisoned by OP and surviving owing to mechanical ventilation.