Initiation and progression of axonopathy in experimental autoimmune encephalomyelitis.
Axonal loss is the principal cause of chronic disability in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). In C57BL/6 mice with EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide 35-55, the first evidences of axonal damage in spinal cord were in acute subpial and perivascular foci of infiltrating neutrophils and lymphocytes and included intra-axonal accumulations of the endovesicular Toll-like receptor TLR8, and the inflammasome protein NAcht leucine-rich repeat protein 1 (NALP1). Later in the course of this illness, focal inflammatory infiltrates disappeared from the spinal cord, but there was persistent activation of spinal cord innate immunity and progressive, bilaterally symmetric loss of small-diameter corticospinal tract axons. These results support the hypothesis that both contact-dependent and paracrine interactions of systemic inflammatory cells with axons and an innate immune-mediated neurodegenerative process contribute to axonal loss in this multiple sclerosis model.
Soulika
Athena M
AM
Institute for Pediatric Regenerative Medicine, University of California Davis School of Medicine, Sacramento, California 95817, USA.
Lee
Eunyoung
E
McCauley
Erica
E
Miers
Laird
L
Bannerman
Peter
P
Pleasure
David
D
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D007113:Immunity, Innate / Q000276:immunology; D007962:Leukocytes / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D011712:Pyramidal Tracts / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D014855:Wallerian Degeneration / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C529636:NALP1 protein, mouse; D051200:Toll-Like Receptor 8