Sural Nerve Perfusion in Mice.

Anete Dudele,Peter Mondrup Rasmussen,Leif Østergaard

doi:10.3389/fnins.2020.579373

Abstract

Peripheral nerve function is metabolically demanding and nerve energy failure has been implicated in the onset and development of diabetic peripheral neuropathy and neuropathic pain conditions. Distal peripheral nerve oxygen supply relies on the distribution of red blood cells (RBCs) in just a few, nearby capillary-sized vessels and is therefore technically challenging to characterize. We developed an approach to characterize distal sural nerve hemodynamics in anesthetized, adult male mice using in vivo two-photon laser scanning microscopy. Our results show that RBC velocities in mouse sural nerve vessels are higher than those previously measured in mouse brain, and are sensitive to hindlimb temperatures. Nerve blood flow, measured as RBC flux, however, was similar to that of mouse brain and unaffected by local temperature. Power spectral density analysis of fluctuations in RBC velocities over short time intervals suggest that the technique is sufficiently sensitive and robust to detect subtle flow oscillations over time scales from 0.1 to tens of seconds. We conclude that in vivo two-photon laser scanning microscopy provides a suitable approach to study peripheral nerve hemodynamics in mice, and that local temperature control is important during such measurements.

Highlights

Nerve blood flow is important for peripheral nerve function and nerve blood flow deficits have been implicated in peripheral nerve pathologies, e.g., diabetic peripheral neuropathy (DPN) and neuropathic pain conditions (Cameron and Cotter, 1997; Lim et al, 2015)
Even though the relatively short recoding lengths of 30 s limit the strength of conclusions that can be derived from the changes in oscillations in RBCv signal, the analysis shows that local blood flow control in the nerve is affected by changing temperatures and by Mean arterial pressure (MAP)
The novel peripheral nerve window technique presented here is suitable for detailed investigation of sural nerve hemodynamics in mice

Summary

Introduction

Nerve blood flow is important for peripheral nerve function and nerve blood flow deficits have been implicated in peripheral nerve pathologies, e.g., diabetic peripheral neuropathy (DPN) and neuropathic pain conditions (Cameron and Cotter, 1997; Lim et al, 2015). Unlike the brain, peripheral nervous tissue is not prone to ischemic injury, partly due to its redundant, segmental blood supply and high overall ischemic tolerance. It takes as long as 1–3 h of ischemia to induce permanent axonal damage in peripheral nerves (Zochodne, 2018). Peripheral nerves affected by diabetes are more sensitive to ischemic damage and this has been attributed to chronic insufficient oxygenation due to capillary dysfunction (Østergaard et al, 2015)

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