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The Journal of Neuroscience, April 14, 2004, 24(15):3752-3761; doi:10.1523/JNEUROSCI.0406-04.2004

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Neurobiology of Disease
Passive or Active Immunization with Myelin Basic Protein Impairs Neurological Function and Exacerbates Neuropathology after Spinal Cord Injury in Rats

T. Bucky Jones,¹ Daniel P. Ankeny,³ Zhen Guan,³ Violeta McGaughy,³ Lesley C. Fisher,² D. Michele Basso,^1,2 and Phillip G. Popovich^1,3

¹The Neuroscience Graduate Studies Program, Division of Physical Therapy, ²School of Allied Medical Professions, and ³Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210

Myelin-reactive T-cells are activated by traumatic spinal cord injury (SCI) in rodents and humans. Despite the historical association of these cells with experimental and clinical neuropathology, recent data suggest a neuroprotective role for myelin-reactive T-cells. Because of the biological and therapeutic implications of these findings, we attempted to reproduce the original neuroprotective vaccine protocols in a model of rat SCI. Specifically, MBP-reactive T-cell function was enhanced in SCI rats via passive or active immunization. Locomotor function was assessed using a standardized locomotor rating scale (Basso–Beattie–Bresnahan scale) and was correlated with myelin and axon sparing. The functional and anatomical integrity of the rubrospinal pathway also was analyzed using the inclined plane test and anatomical tract tracing. MBP-immunized rats exhibited varying degrees of functional impairment, exacerbated lesion pathology, greater rubrospinal neuron loss, increased intraspinal T-cell accumulation, and enhanced macrophage activation relative to SCI control groups. These data are consistent with the conventional view of myelin-reactive T-cells as pathological effector cells.

Key words: inflammation; autoimmunity; neuroprotection; vaccine; myelin basic protein; EAE

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Received Feb 4, 2004; revised March 5, 2004; accepted March 7, 2004.

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