Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats.
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.
Jones
T Bucky
TB
The Neuroscience Graduate Studies Program, Division of Physical Therapy, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Ankeny
Daniel P
DP
Guan
Zhen
Z
McGaughy
Violeta
V
Fisher
Lesley C
LC
Basso
D Michele
DM
Popovich
Phillip G
PG
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007116:Immunization, Passive / Q000379:methods*; D009043:Motor Activity / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology; D009187:Myelitis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014611:Vaccination / Q000379:methods*
D004676:Myelin Basic Protein