The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury

R. H. Singleton, J. R. Stone, D. O. Okonkwo, A. J. Pellicane, J. T. Povlishock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The immunophilin ligand, cyclosporin A (CsA), is effective in reducing the axonal damage associated with traumatic brain injury (TBI). Based upon extensive ultrastructural and immunohistochemical studies, the neuroprotection afforded by CsA appeared to be mediated via mitochondrial protection, specifically, the prevention of mitochondrial swelling and inhibition of mitochondrial permeability transition (MPT). However, the potential that CsA could also be neuroprotective via the immunophilin-mediated inhibition of the protein phosphatase, calcineurin (CN) has not been directly assessed. To address this issue, the current study assessed the ability of FK506, another immunophilin ligand that inhibits CN with no effect on MPT, to attenuate axonal damage in a rat impact-acceleration model of TBI. Traumatic axonal injury (TAI), detected via an antibody against β-amyloid precursor protein (APP), a specific marker of axonal injury, was significantly reduced at 24 hr postinjury in Sprague-Dawley rats receiving intravenous FK506 (2 mg/kg; n = 5) 30 min prior to injury compared to vehicle controls (n = 3). While not rejecting the established efficacy of CsA in providing neuroprotection via its targeting of MPT, this study does underscore the potential importance of CN in the progressive pathobiology of TAI, suggesting that CN may constitute another important therapeutic target.

Original languageEnglish
Pages (from-to)607-614
Number of pages8
JournalJournal of Neurotrauma
Issue number6
StatePublished - 2001
Externally publishedYes


  • Amyloid precursor protein
  • Cytoskeleton
  • Immunocytochemistry
  • Immunophilin
  • Rat
  • Traumatic axonal injury
  • Traumatic brain injury


Dive into the research topics of 'The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury'. Together they form a unique fingerprint.

Cite this