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PMID: 10964948 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 17 ·2000-09-01 ·Pages 6421-30

Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, Leibowitz-Amit R, Pevsner E, Akselrod S, Neeman M, Cohen IR, Schwartz M

Abstract

Partial injury to the spinal cord can propagate itself, sometimes leading to paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS antigen myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in rats. Here we show that not only transfer of T cells but also active immunization with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, using the New York University impactor, were injected systemically with anti-MBP T cells at the time of contusion or 1 week later. Another group of rats was immunized, 1 week before contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional recovery was assessed in a randomized, double-blinded manner, using the open-field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of contusion at T7 differed from that at T9 (2.9+/-0.4, n = 25, compared with 8.3+/-0.4, n = 12; p<0.003). In both cases, a single T cell treatment resulted in significantly better recovery than that observed in control rats treated with T cells directed against the nonself antigen ovalbumin. Delayed treatment with T cells (1 week after contusion) resulted in significantly better recovery (7.0+/-1; n = 6) than that observed in control rats treated with PBS (2.0+/-0.8; n = 6; p<0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score of 6.1+/-0.8 (n = 6) compared with a score of 3.0+/-0.8 (n = 5; p<0.05) in control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical staining, and diffusion anisotropy magnetic resonance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, achieved by either adoptive transfer or active immunization, enhances recovery from spinal cord injury by conferring effective neuroprotection. The autoimmune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factors whose production is locally regulated.

MeSH Terms
Animals Female Guinea Pigs Immunization, Passive Lymphocyte Transfusion Myelin Basic Protein/immunology Ovalbumin/immunology Rats Rats, Inbred Lew Red Nucleus/pathology,physiopathology Spinal Cord Injuries/immunology,physiopathology,therapy T-Lymphocytes/immunology Time Factors
Chemicals
Myelin Basic Protein Ovalbumin
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Hauben E
Departments of Neurobiology, Immunology, and Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Butovsky O
Nevo U
Yoles E
Moalem G
Agranov E
Mor F
Leibowitz-Amit R
Pevsner E
Akselrod S
Neeman M
Cohen I R
Schwartz M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
2000-09-01
Pages
6421-30
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772980
Subset
IM
Corrections
ErratumIn
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External Links
PubMed source PMC Full Text View journal details
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