Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations.

Michael Punsoni,Thomas Palaia,Mark M Stecker,Matthew Stevenson,Steven Drexler

doi:10.1002/brb3.347

Abstract

IntroductionThe response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves.MethodsSciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment. After the experiment, light microscopy and electron microscopy were performed.ResultsLight microscopic images showed mild changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal swelling while hyperglycemic anoxia produced apparent changes in the myelin. Anoxic changes were not uniform in all axons. Electron microscopy showed only minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the extremes of glucose concentration especially with hyperglycemia, there was a more severe disruption of intermediate filaments and loss of axonal structure with anoxia. Hypothermia protected axons from the effect of anoxia and produced peak axonal swelling in the 17–30°C range.ConclusionsThe combination of hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal disruption. Changes in axonal diameter are complex and are influenced by many factors.

Highlights

The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature
The physiology of the in-vitro sciatic nerve model is wellstudied and the current study provides the anatomic correlate of the physiologic changes those that occur when peripheral nerve is exposed to anoxia and different glucose concentrations
When nerves are exposed to anoxia there is axonal swelling and disruption of the cytoskeleton as found previously in Waxman’s in-vitro study of rat optic nerve (Waxman et al 1992) and these changes are seen in the present study of rat sciatic nerve

Summary

Introduction

The peripheral nerve can be damaged by many physical stresses including trauma, toxins, and anoxia (Stys 2005) These injuries can be probed with physiological studies (Weigl et al 1989; Bostock et al 1994; Kiernan et al 2002; Stecker et al 2011, 2013a,b), biochemical studies (Okada and McDougal 1971; Hofteig et al 1981; Brown et al 2012; Stavniichuk et al 2012), and histopathological studies (Def Webster and Ames 1965; Nukada and Dyck 1987; Dyck et al 1990; Edmonds and Koenig 1990; Waxman et al 1992) among others. There are other histological changes seen such as breakdown of the cytoskeleton (Waxman et al 1994) and swelling of mitochondria (Def Webster and Ames 1965) Correlating these histologic changes with neurophysiologic changes in the function of the nerve is an important step in creating a more accurate,. Exploring the effects of hyperglycemia on the response to anoxia can provide a better understanding of neuropathies that are clearly related to anoxia and hyperglycemia such as critical illness polyneuropathy (Bolton 2005) and possibly diabetic neuropathy (Dyck 1989)

Materials and Methods

Results

Discussion