An animal model of chronic ischemic neuropathy with proliferative changes of nerve microvessel wall

In order to produce a model of ischemic neuropathy with neural microvascular alterations, sodium laurate was injected into a femoral artery and saline into the contralateral artery at the mid-thigh level in Sprague-Dawley rats aged 11 weeks. In view of the dose-related findings, 0.3 mg sodium laurate dissolved in 0.1 ml saline was used for the main experiment. The laurate-injected leg showed paresis during the experimental period. On day 1-7, various stages of Wallerian degeneration and acute microvascular changes were found. At 1 month, regenerating myelinated nerve fibers (MNFs) were found at the central or total fascicular area mainly in the distal tibial nerve. Morphometric analyses suggested that MNFs other than regenerating fibers are atrophic ones. The proliferative changes of nutrient microvascular walls were striking. The percent of closed epineurial microvessels was significantly larger on the laurate-injected sides and inversely associated with the diameter of MNFs. At 7 months, the attenuation of MNFs was more prominent and microvascular alterations were persistently observed. These pathological findings resemble those of chronic ischemic neuropathy including diabetic neuropathy, suggesting that this neuropathy model might provide some valuable and useful clues for clarifying the pathogenesis of chronic ischemic neuropathy.