The therapeutic window after spinal cord injury can accommodate T cell-based vaccination and methylprednisolone in rats.
Immune system activity has traditionally been considered harmful for recovery after spinal cord injury (SCI). Recent evidence suggests, however, that immune activity--and specifically autoimmune activity--is evoked by the insult, is beneficial if properly regulated and is amenable to boosting. Thus, for example, vaccination with an altered peptide ligand derived from myelin basic protein reduces the progressive degeneration of neurons that escaped the initial insult, thereby promoting recovery after SCI. As the steroid drug methylprednisolone (MP) is currently the only treatment available for patients with SCI, our purpose in the present study was to examine the mutual compatibility of the two treatments within the post-traumatic therapeutic window. We show, using rats of two different strains, that if MP is injected concomitantly with the therapeutic vaccination, the beneficial effect of the vaccination is diminished. However, if MP is given immediately after the insult and the vaccination 48 h later, MP does not detract from the beneficial effect of the vaccination. These results demonstrate that the therapeutic window after SCI can accommodate immediate administration of MP plus a delayed therapeutic vaccination.
Ibarra
Antonio
A
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel. iantonio65@yahoo.com
Hauben
Ehud
E
Butovsky
Oleg
O
Schwartz
Michal
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003911:Dextrans; D053331:Ectodysplasins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D016233:Immunotherapy, Active / Q000379:methods*; D007796:Laminectomy / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D008775:Methylprednisolone / Q000627:therapeutic use*; D009043:Motor Activity / Q000502:physiology; D009161:Mycobacterium / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012235:Rhodamines; D013045:Species Specificity; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000276:immunology
D003911:Dextrans; D053331:Ectodysplasins; C067661:Fluoro-Ruby; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012235:Rhodamines; C115314:myelin basic protein 87-99; C009966:N-(2-naphthalene)sulfonyl-DL-tryptophan; D014364:Tryptophan; D008775:Methylprednisolone