FK506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat

Rubèn López-Vales, Guillermo García-Alías, Joaquim Forés, Esther Udina, Bruce G. Gold, Xavier Navarro, Enrique Verdú

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50 Citations (Scopus)

Abstract

We examined the efficacy of FK506 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), FK506 (2 mg/kg), or saline. An additional group received an initial bolus of FK506 (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 post-operation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEG, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 1β (IL-1β) immunoreactivity were quantified in the injured spinal cord. FK506-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 FK506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK506 compared to that in animals given MP or saline, whereas IL-1β expression was similarly reduced in both FK506- and MP-treated groups. Microglia/macrophage response was reduced in FK506 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 FK506 improved functional and histologic results to a greater degree than did a single bolus of FK506. The results indicate that FK506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries. © 2005 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)827-836
JournalJournal of Neuroscience Research
Volume81
DOIs
Publication statusPublished - 15 Sep 2005

Keywords

  • FK506
  • Inflammation
  • Methylprednisolone
  • Spinal cord injury
  • Tissue sparing

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