The progression and recovery of neurotoxicity induced by a single oral dose of aniline in rats

Abstract

This study was performed in order to identify the recovery from paralytic gait and hindlimb paralysis in rats that were treated once with 1000 mg/kg of aniline. Additionally, spongy change in the white matter of the spinal cord were chronologically examined in order to clarify the morphologic events in the lesions of the aniline-treated rats, which were killed on days 4, 8, 12, 15, 22, 30, and 60, Paralytic gait first appeared at day 8. The incidence of the paralytic gait and hindlimb paralysis increased in the following 4 days, and then decreased by day 19. Spongy change in the white matter of the spinal cord was first detected on day 8 in the histopathologic examination. The spongy state was due to splitting of the intraperiod line of the myelin sheath at the ultrastructural level. The incidence and severity of the lesions increased by day 12 or day 15, and then the spongy state repaired markedly by day 60. In the electron microscopic examination, the membranous aggregates in the cytoplasm of oligodendrocytes in the white matter of the spinal cord were detected on day 4, prior to the appearance of spongy change in this area. The immunoreactivity to anti-transferrin (Tf) antibody is an indicator of mature oligodendrocyte, metabolically supporting myelin. The decreased Tfimmunoreactivity of the oligodendrocytes was found in the aniline-treated rats that were killed on day 4. This result suggests the dysfunction of oligodendrocytes with respect to the myelin turnover. Remyelination in the lesions was apparent on day 22, according with the processes of the disappearance of membranous aggregates in the oligodendrocytes and the processes of the recovery of the Tf-immunoreactivity of the oligodendrocytes. Our results suggest that the possible primary target of aniline neurotoxicity is oligodendrocytes. and that the affected rats are able to recover spontaneously from this neurotoxicity.