Myelin/axonal pathology in interleukin-12 induced serial relapses of experimental allergic encephalomyelitis in the Lewis rat.
Lewis rats, on recovery from monophasic clinical experimental allergic encephalomyelitis (EAE), can be induced to develop repeated paralytic relapses with a graded reduction in clinical severity following intraperitoneal administration of IL-12. By the time of the third relapse, the number and size of inflammatory cuffs in the spinal cord were reduced with the makeup of the cellular infiltrate shifting to a significantly increased number of B cells. Serum levels of myelin basic protein (MBP)-specific IgG1 and IgG2b were found to rise over time while MBP and MBP peptide-positive macrophages and microglia became evident in perivascular cuffs and in spinal cord parenchyma, indicative of myelin phagocytosis. Axonal death was observed in semithin and EM sections of spinal cord in third relapse animals in association with iNOS and tPA immunostaining throughout gray and white matter. These neurotoxic or excitotoxic agents may contribute to axonal damage directly or indirectly by activated microglia and macrophages, leading to limited damage of the axonal-myelin unit.
Ahmed
Z
Z
Neuroinflammation Group, Department of Neurochemistry, Institute of Neurology, University College London, London, United Kingdom. z.ahmed@ion.ucl.ac.uk
Gveric
D
D
Pryce
G
G
Baker
D
D
Leonard
J P
JP
Cuzner
M L
ML
Diemel
L T
LT
D000208:Acute Disease; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001369:Axons / Q000737:chemistry / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry; D018664:Interleukin-12; D007378:Interleukins / Q000097:blood; D007958:Leukocyte Count; D008262:Macrophage Activation; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000473:pathology*; D010243:Paralysis / Q000139:chemically induced; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D013116:Spinal Cord / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D001323:Autoantibodies; D007074:Immunoglobulin G; D007378:Interleukins; D004676:Myelin Basic Protein; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D010959:Tissue Plasminogen Activator