Do Denervated Peripheral Nerve Trunks Become Ischemic? The Impact of Chronic Denervation on Vasa Nervorum

Abstract

The long-term relationship between the peripheral nerve trunk and its vascular supply, the vasa nervorum, has not been considered in the context of denervation and regeneration. While the microvessels of peripheral nerve are not thought to influence Wallerian degeneration itself, in this work we explored how vasa nervorum respond to denervation of the nerve trunk. Our hypotheses were that the presence of axons had a significant impact on the vasa nervorum and that the absence of reinnervation might eventually lead to an unfavorable ischemic regenerative microenvironment. We studied rat sciatic nerve trunks for up to 6 months following transection and either prevented regeneration or allowed it to proceed. Vasa nervorum were studied in several ways: (i) measurements of local endoneurial blood flow using microelectrode hydrogen clearance polarography; (ii) measurements of erythrocyte flux (flow) in the extrinsic nerve plexus using laser Doppler flowmetry; (iii) India ink perfusion of microvessels in unfixed nerve; (iv) mRNA expression of vascular endothelial growth factor (VEGF) using reverse transcription polymerase chain reaction. Early after injury, there were rises in endoneurial and extrinsic flow, microvessel numbers, and VEGF mRNA expression. Angiogenesis was apparently confined to the epineurial and perineurial compartments. Later, however, there were substantial declines in flow observed in long-term (6-month) denervated sciatic nerve trunks associated with declines in the caliber of new microvessels. Reinnervated sciatic nerves had restored endoneurial blood flow. The findings confirm important relationships between axon presence and local blood flow. Angiogenesis is a feature of the injured peripheral nerve, but long term denervated nerve trunks have declines of flow despite retaining new microvessels.