Targeting experimental autoimmune encephalomyelitis lesions to a predetermined axonal tract system allows for refined behavioral testing in an animal model of multiple sclerosis.
In multiple sclerosis (MS) the structural damage to axons determines the persistent clinical deficit patients acquire during the course of the disease. It is therefore important to test therapeutic strategies that can prevent or reverse this structural damage. The conventional animal model of MS, experimental autoimmune encephalomyelitis (EAE), typically shows disseminated inflammation in the central nervous system, which leads to a clinical deficit that cannot be directly attributed to a defined tract system. For this reason we have developed a localized EAE model, in which large inflammatory lesions are targeted to the dorsal columns of the spinal cord, an area including the corticospinal tract. These lesions show the pathological hallmarks of MS plaques and lead to reproducible and pronounced deficits in hindlimb locomotion. Because of the anatomical specificity of this technique we can now use highly sensitive behavioral tests that assess the functional integrity of specific axonal tracts. We show that these tests are predictive of the site and extent of a given lesion and are more sensitive for assessing the clinical course than the scales commonly used for disseminated EAE models. We believe that this targeted EAE model will become a helpful new tool for the evaluation of therapeutic approaches for MS that attempt to protect axons or support their repair.
Kerschensteiner
Martin
M
Brain Research Institute, University of Zurich, and the Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland. martink@pcg.wustl.edu
Stadelmann
Christine
C
Buddeberg
Bigna S
BS
Merkler
Doron
D
Bareyre
Florence M
FM
Anthony
Daniel C
DC
Linington
Christopher
C
Brück
Wolfgang
W
Schwab
Martin E
ME
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007278:Injections, Spinal; D007371:Interferon-gamma / Q000008:administration & dosage; D008124:Locomotion / Q000502:physiology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011712:Pyramidal Tracts / Q000473:pathology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma