Hexachlorophene-induced myelin lesions in the amphibian central nervous system: A freeze-fracture study

Abstract

Myelin membranes in the optic nerves and spinal cord of Xenopus laevis tadpoles were studied with the freeze-fracture technique during the pathogenesis of edematous lesions induced by hexachlorophene (HCP) intoxication. Freeze-fracture replicas of myelin exposed to HCP for as long as 12 days revealed that even chronic intoxication did not significantly alter particle strands associated with zonulae occludentes between tongue processes and their adjacent layers of myelin. Furthermore, experiments using electron-dense tracers demonstrated that the permeability characteristics of these junctions were unchanged. Following subcutaneous perineural injection of lanthanum or horseradish peroxidase (HRP), the tracers easily penetrated the optic nerve and were uniformly distributed throughout its parenchyma. While only limited amounts of lanthanum could penetrate myelin and enter the vacuoles, no HRP was found within the large myelin vacuoles after either brief or long-term exposure to HCP. In contrast to the tight junctions, some modifications were observed in the distribution of other intramembranous particles associated with myelin lamellae adjacent to swollen regions of the sheath. These alterations primarily involved formation of multifocal, particle-free elevations which corresponded to areas in which the fused inner glial leaflets, forming the major dense line, had separated. Such particle-deficient areas were absent in myelin of control as well as normal sheaths of HCP-intoxicated animals. Thus, these findings demonstrated that the structural and physiological characteristics of a tight junctional component of myelin were not affected by HCP. Sparing of these junctions may account for the relatively low incidence of demyelination and reversible nature of HCP lesions. The development of particle-deficient blisters on glial leaflets suggests, however, that HCP may be capable of modifying other aspects of the chemical organization of myelin, thereby producing local alterations in the compact arrangement of myelin lamellae.