SARIN-INDUCED NEUROPATHOLOGY IN RATS

Sarin, a highly toxic cholinesterase (ChE) inhibitor, administered at near 1 LD(50) dose causes severe signs of toxic cholinergic hyperactiv ity in both the peripheral and central nervous systems (CNS). The pres ent study evaluated acute and long-term neuropathology following expos ure to a single LD(50) dose of sarin and compared it to lesions caused by equipotent doses of soman described previously. Rats surviving 1 L D(50) dose of sarin (95 mu g/kg; IM), were sacrificed at different tim e intervals post exposure (4 h-90 days) and their brains were taken fo r histological and morphometric study. Lesions of varying degrees of s everity were found in about 70% of the animals, mainly in the hippocam pus, piriform cortex, and thalamus. The damage was exacerbated with ti me and at three months post exposure, it extended to regions which wer e not initially affected. Morphometric analysis revealed a significant decline in the area of CA1 and CA3 hippocampal cells as well as in th e number of CA1 cells. The neuropathological findings, although genera lly similar to those described following 1 LD(50) soman, differed in s ome features, unique to each compound, for example, frontal cortex dam age was specific to soman poisoning. It is concluded that sarin has a potent acute and long-term central neurotoxicity, which must be consid ered in the design of therapeutic regimes.