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ADMINISTRATION OF 3,3'-IMINODIPROPIONITRILE TO THE RAT RESULTS IN REGION-DEPENDENT DAMAGE TO THE CENTRAL NERVOUS SYSTEM AT LEVELS ABOVE THE BRAIN STEM
Citation:
Llorens, J., K. Crofton, AND J. O'Callaghan. ADMINISTRATION OF 3,3'-IMINODIPROPIONITRILE TO THE RAT RESULTS IN REGION-DEPENDENT DAMAGE TO THE CENTRAL NERVOUS SYSTEM AT LEVELS ABOVE THE BRAIN STEM. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/025 (NTIS PB94137296), 1993.
Description:
The neurotoxicant 3,3'-iminodipropionitrile (IDPN) induces a persistent neurological syndrome and an axonopathic condition. n this study, the concentration of glial fibrillary acidic protein (GFAP), measured by solid-phase radioimmunoassay in brain tissue homogenates, was used as a marker of the reactive gliosis occurring in the central nervous system after IDPN intoxication. ale Long-Evans rats were given 3 daily i.p. injections of 0 - 600 mg/kg/day of IDPN in saline. even days after 3 x 400 mg/kg/day, GFAP increases were observed in ponsmedulla, midbrain, and cerebral cortex, but not in cerebellum, hypothalamus, hippocampus and striatum. ose-dependent increases in GFAP were observed in cortex at 10 days after administration, whereas no GFAP response was observed in the cerebellum of the same animals. FAP increases were obtained in either cingulate, frontal, parietal and occipital-temporal cortical areas 10 days after 3 x 400 mg/kg/day. arge effect was also observed in olfactory bulbs at the same dose and time. he effect of the 3 x 400 mg/kg/day treatment on cingulate cortex GFAP was observed to have a rapid onset, with a peak around one week, and a recovery to basal levels within two weeks after administration. he present results demonstrate region specific, dose- and time-dependent increases in GFAP in the CNS of rats exposed to IDPN.