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Titolo:
The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury
Autore:
Singleton, RH; Stone, JR; Okonkwo, DO; Pellicane, AJ; Povlishock, JT;
Indirizzi:
Virginia Commonwealth Univ, Med Coll Virginia, Dept Anat, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Univ Virginia, Dept Neurosurg, Charlottesville, VA USA Univ Virginia Charlottesville VA USA Neurosurg, Charlottesville, VA USA
Titolo Testata:
JOURNAL OF NEUROTRAUMA
fascicolo: 6, volume: 18, anno: 2001,
pagine: 607 - 614
SICI:
0897-7151(200106)18:6<607:TILFAA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
MICROTUBULE-ASSOCIATED PROTEIN-2; CYCLOSPORINE-A; NEUROFILAMENT PROTEINS; PHOSPHORYLATION STATE; HEAD-INJURY; TAU-FACTOR; IN-VIVO; DAMAGE; CALCINEURIN; PERMEABILITY;
Keywords:
amyloid precursor protein; cytoskeleton; immunocytochemistry; immunophilin; rat; traumatic axonal injury; traumatic brain injury;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Povlishock, JT Virginia Commonwealth Univ, Med Coll Virginia, Dept Anat, 1101 E Marshall St,Campus Virginia Commonwealth U, Richmond, VA 23298 USA Virginia Commonwealth Univ 1101 E Marshall St,Campus Virginia Commonwealth U Richmond VA USA 23298
Citazione:
R.H. Singleton et al., "The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury", J NEUROTRAU, 18(6), 2001, pp. 607-614

Abstract

The immunophilin ligand, cyclosporin A (CsA), is effective in reducing theaxonal damage associated with traumatic brain injury (TBI). Based upon extensive ultrastructural and immunohistochemical studies, the neuroprotectionafforded 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 beta -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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:33:52