The Sequential Alterations of Endoneurial Cholesterol and Fatty Acid in Wallerian Degeneration and Regeneration

Abstract

The endoneurial nonpolar lipids were serially examined throughout Wallerian degeneration and regeneration. Following nerve crush in the rat, the endoneurial content of cholesterol falls and cholesteryl ester content rises dramatically. The maximal alteration of this ratio corresponds reasonably well with events of myelin ovoid dissolution to sudanophilic amorphous lipids. Thereafter, as regenerative events overshadow degenerative events the ratio is slowly restored toward normal. The increased cholesteryl esters are probably synthesized within endoneurium from free fatty acids which become available when myelin is degraded. The endoneurial free fatty acid content presumably represents the net effect of phospholipid degradation, cholesterol esterification, cholesteryl ester hydrolysis, and fascicular entry and exit. Free fatty acids become significantly elevated by 12 days, probably reach a peak between 16 and 60 days, and thereafter return to normal with fiber regeneration. The fatty acid composition of cholesteryl esters from crushed nerves is markedly different from those of normal sciatic nerves. The altered fatty acid composition of cholesteryl esters from myelin suggests that both synthesis and hydrolysis exhibit substrate specificity toward chain length and unsaturation, with oleate being the most favored substrate.

A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve.

“…The cholesterol stores of these myelinating cells presumably had been used to synthesize the myelin that now enveloped the axons. This is in agreement with biochemical measurements that show that cholesteryl esters in the injured nerve decline after the second and third weeks (39). The cho-~~~~~~~~~~~~~~~~~.…”

“…Our data now show that these cholesteryl esters are depleted first in Schwann cells and then in macrophages and neurolemmal fibroblasts. Previous lipid analyses had shown that much of the free cholesterol originally in degenerating myelin is never stored as cholesteryl esters; high levels of free cholesterol persist in the injured nerve (39). Our study demonstrates that myelin degradation is completed as new myelin forms.…”

“…Numerous lipid droplets had already accumulated within Schwann cells and resident macrophages (Fig. 4 A); based on previous biochemical studies, these droplets probably are cholesteryl esters (36)(37)(38)(39).…”

“…Such cholesterol-rich apoE-containing lipoproteins bind with high affinity to the LDL receptor (6, (39). Cholesteryl esters are most abundant in the nerve during the second week after injury and decline in the fourth week (39). Our data now show that these cholesteryl esters are depleted first in Schwann cells and then in macrophages and neurolemmal fibroblasts.…”

“…These HDL acquire apoE along with cholesterol and lose apoA-I (10,11). Such cholesterol-rich apoE-containing lipoproteins bind with high affinity to the LDL receptor (6, (39). Cholesteryl esters are most abundant in the nerve during the second week after injury and decline in the fourth week (39).…”