Angiogenesis at the site of neuroma formation in transected peripheral nerve

Abstract

Investiture of new microvessels within an injured peripheral nerve trunk may determine the success that the local environment has in promoting axonal sprouting and regeneration. We therefore examined microvessel investment of 24 h–14 d proximal nerve stump preparations in rat sciatic nerves. The stumps, later destined to form neuromas, were created by sciatic nerve transection with resection of distal branches to prevent distal reinnervation. Microvessels were studied in the proximal stump in semithin whole mount sections of nerve and by analysis of India ink perfused microvessel profiles. Quantitative image analysis was made of the luminal profiles of vessels perfused with India ink from unfixed sections of the stumps, contralateral uninjured nerves and sham-exposed but uninjured nerves. Evidence of angiogenesis was observed in stumps 7 d after transection, indicated by a rise in the total numbers of perfused microvessels and in the numbers of 2–6 μm diameter perfused microvessels. There was a shift in the histogram of the percentage of perfused microvessels towards the 2–4 μm range and a reduction in the mean microvessel luminal area in the stumps. By 14 d, new microvessels were larger, indicated by an increase in total luminal area. New microvessels were prominent in the epineurial connective tissue or between layers of perineurial cells of former fascicles. Microvessels probably share a battery of trophic signals with other proliferating cellular elements in the milieu of the injured peripheral nerve trunk.