title: Glatiramer acetate immune system augmentation for peripheral nerve regeneration in rat crushed sciatic nerve model.
abstract: BACKGROUND
  Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration.
  
  
  METHODS
  Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count).
  
  
  RESULTS
  Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups.
  
  
  CONCLUSIONS
  We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.
authors.affiliation: Department of Orthopaedics and Sports Medicine, University Medical Center, University of Washington School of Medicine, Seattle, WA 98195-6500, USA. shail@hadassah.org.il
authors.forename: Shai
authors.initials: S
authors.lastname: Luria
authors.forename: Thanapong
authors.initials: T
authors.lastname: Waitayawinyu
authors.forename: James
authors.initials: J
authors.lastname: Conniff
authors.forename: H Josette
authors.initials: HJ
authors.lastname: Morton
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Nemechek
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.forename: Leonid I
authors.initials: LI
authors.lastname: Katolik
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Trumble
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068717:Glatiramer Acetate; D007111:Immunity, Cellular / Q000187:drug effects*; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000294:innervation; D009416:Nerve Regeneration / Q000187:drug effects* / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000276:immunology / Q000293:injuries* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D010455:Peptides; D000068717:Glatiramer Acetate