Survival, development, and electrical activity of central nervous system myelinated axons exposed to tumor necrosis factor in vitro

Abstract

Spinal cord explants from CD-1 mouse embryos were cultured in Maximow slide assemblies to promote myelin development. At about 20 days in vitro, recombinant human or mouse tumor necrosis factor alpha (TNF alpha) was added. Observed 3-8 days later, myelin was largely intact. The myelin blistering and oligodendrocyte damage seen in other strains were generally absent. Axonal conduction was measured optically through the use of a voltage-sensitive dye. Action potential shape, conduction velocity, and refractory period were all unchanged by exposure to TNF alpha. Two series of explants were grown with TNF alpha present continuously throughout the culture period. Observed with light and electron microscopy, myelin developed in at least 50% of the explants treated with recombinant mouse TNF alpha and 80% of those exposed to recombinant human TNF alpha. Optically recorded action potentials were of normal shape and refractory period. Conduction velocities were slightly lower than controls. CD-1 mouse central nervous system contains TNF alpha receptors and yet was resistant to myelin damage. The apparent strain specificity of TNF alpha disruption of myelin may result from more indirect modes of action, including interaction with other cytokines produced by glial cells. Survival of axonal conduction suggests that Na+ channel function remains intact following TNF alpha exposure.