Vascular Lesion in the Meninx and Retina Following Administration of 3,3'-Iminodipropionitrile (IDPN) in Rats

Abstract

3,3'-Iminodipropionitrile (IDPN) is a potent neurotoxicant, which produces behavioral abnormalities and neuropathologic lesions in the central and peripheral nervous systems. Recently, 11 laboratories including ours carried out a collaborative neurotoxicity study using IDPN, and arterial hyalinization in the meninx of the brain and spinal cord was detected in 6 laboratories. Before that study, IDPN-induced vascular lesion had not been reported in any organ except the retina. The present study was undertaken to confirm the reproducibility of the IDPN-induced vascular lesion, to find out the onset of the lesion, and to determine the systemic distribution of the lesion. Male Crj:CD(SD)IGS rats were treated daily with IDPN 125 mg/kg and were sacrificed on days 15, 30, and 44. Behavioral abnormalities appeared from day 9 and thereafter, and axonal swelling in the central nervous system (CNS) was found on days 15, 30, and 44. Arterial hyalinization in the meninx was seen in 4 and 5 out of 6 rats on days 30 and 44, respectively. Almost all lesions were found in the small sized arteries in the basilar area of the brain and spinal cord, and near the dorsal roots of the spinal cord. Some affected vessels demonstrated fibrinoid degeneration, inflammatory cell infiltration or occluded lumina due to intimal thickening. In the organs and tissues other than the CNS, arterial hyalinization in the retina was found on days 30 and 44. Our results demonstrate the reproducibility of IDPN-induced vascular lesions and suggest that the lesions characterized by arterial hyalinization are restricted to the CNS and retina, and that vascular lesion occurred following neurotoxicity.