Effect of MOG sensitization on somatosensory evoked potential in Lewis rats.
Myelin oligodendrocyte glycoprotein (MOG) is commonly used as an immunogen to induce an immune response against endogenous myelin, thereby modeling multiple sclerosis in rodents. When MOG is combined with complete Freund's adjuvant (CFA), multifocal, multiphasic disease ensues; whereas when MOG is combined with incomplete Freund's adjuvant (IFA), clinical disease is usually absent. MOG-IFA immunized animals can be induced to have neurological disease after intraspinal injections of cytokines and ethidium bromide (EtBr). In this study, we investigated whether MOG-IFA immunized rats exhibited subclinical injury as defined by somatosensory evoked potential (SEP) recordings. The titration of anti-MOG-125 antibodies showed robust peripheral mounting of immune response against myelin in MOG-immunized rats. However the SEP measures showed no significant change over time. Upon injecting cytokine-EtBr in the spinal cord after MOG sensitization, the SEP recordings showed reduced amplitude and prolonged latency, suggestive of axonal injury and demyelination in the dorsal column, respectively. These findings were later confirmed using T2-weighted MRI and histological hematoxylin-eosin stain of the spinal cord. This report establishes that MOG-IFA immunization alone does not alter neuronal conduction in SEP-related neural-pathways and that longitudinal in-vivo SEP recordings provide a sensitive read-out for focal myelitis (MOG-IFA and intraspinal cytokine-EtBr) in rats.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205, United States. hmn@jhu.edu
Angelo H
AH
All
Piotr
P
Walczak
Gracee
G
Agrawal
Michael
M
Gorelik
Christopher
C
Lee
Nitish V
NV
Thakor
Jeff W M
JW
Bulte
Douglas A
DA
Kerr
D000818:Animals; D001921:Brain / Q000473:pathology; D004567:Electrodes, Implanted; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004996:Ethidium / Q000008:administration & dosage / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory / Q000276:immunology*; D005106:Exploratory Behavior; D005260:Female; D005620:Freund's Adjuvant; D007114:Immunization; D007267:Injections; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology; D008124:Locomotion; D008279:Magnetic Resonance Imaging; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D015850:Interleukin-6; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D004996:Ethidium