title: FK 506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat.
abstract: We examined the efficacy of FK 506 in reducing tissue damage after spinal cord injury in comparison to methylprednisolone (MP) treatment. Rats were subjected to a photochemical injury (T8) and were given a bolus of MP (30 mg/kg), FK 506 (2 mg/kg), or saline. An additional group received an initial bolus of FK 506 (2 mg/kg) followed by daily injections (0.2 mg/kg intraperitoneally). Functional recovery was evaluated using open-field walking, inclined plane tests, motor evoked potentials (MEPs), and the H-reflex response during 14 days postoperation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEC, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1 beta) immunoreactivity were quantified in the injured spinal cord. FK 506-treated animals demonstrated significantly better neurologic outcome, higher MEP amplitudes, and lower H-wave amplitude compared to that of saline-treated rats. In contrast, administration of MP did not result in significant differences with respect to the saline-treated group. Histologic examination revealed that tissue sparing was largest in FK 506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK 506 compared to that in animals given MP or saline, whereas IL-1 beta expression was similarly reduced in both FK 506- and MP-treated groups. Microglia/macrophage response was reduced in FK 506 and MP-injected animals at 3 dpo, but only in MP-treated animals at 7 dpo with respect to saline-injected rats. Repeated administrations of FK 506 improved functional and histologic results to a greater degree than did a single bolus of FK 506. The results indicate that FK 506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries.
authors.affiliation: Group of Neuroplasticity and Regeneration, Institute of Neuroscience and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Rubèn
authors.initials: R
authors.lastname: López-Vales
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Alías
authors.forename: Joaquim
authors.initials: J
authors.lastname: Forés
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Gold
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.forename: Enrique
authors.initials: E
authors.lastname: Verdú
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004594:Electrophysiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005911:Gliosis / Q000473:pathology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis; D008775:Methylprednisolone / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016559:Tacrolimus / Q000494:pharmacology*; D016138:Walking
chemical_list: D000893:Anti-Inflammatory Agents; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D016559:Tacrolimus; D008775:Methylprednisolone