Cytokines modulate the inflammatory response and change permissiveness to neuronal adhesion in injured mammalian central nervous system.
Axonal injury of peripheral nerves has been shown to be followed by rapid and massive invasion of the nerves by macrophages, which appear to play an important role in the subsequent ability of these nerves to regenerate. In contrast, macrophage invasion of injured nerves of the central nervous system is limited, and the relationship between the post-traumatic inflammatory response of central nervous system nerves and their poor ability to regenerate is not fully understood. We used the proinflammatory cytokine tumor necrosis factor-alpha and the macrophage growth factor, colony stimulating factor-1, to examine whether the inflammatory response can be augmented in the optic nerve following injury, and whether such augmentation is accompanied by regeneration-associated changes. It appeared that the two cytokines caused a significant increase in the number of macrophages invading the optic nerve immediately after injury. Interestingly, however, in the nerve treated with tumor necrosis factor-alpha (but not in the nerve treated with colony stimulating factor-1) this increase was accompanied by an increased permissiveness of the nerve to neuronal adhesion, which we examined in vitro using longitudinal sections of the nerve on which PC12 cells were seeded. The results are discussed with respect to the ability of tumor necrosis factor-alpha to modify the nonpermissive nature of central nervous system white matter.
Lotan
M
M
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Solomon
A
A
Ben-Bassat
S
S
Schwartz
M
M
D000818:Animals; D015415:Biomarkers; D002448:Cell Adhesion / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve / Q000187:drug effects / Q000502:physiology; D020221:Optic Nerve Injuries; D016716:PC12 Cells; D010586:Phagocytes / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor