FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis

Journal of Neuroscience Research
Bruce G GoldDennis N Bourdette

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) in which demyelination and axonal loss result in permanent neurologic disability. We examined the neuroprotective property of the immunosuppressant FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and cyclosporin A (CsA) in a chronic relapsing experimental autoimmune encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in complete Freund's adjuvant. At the onset of paralysis, 12-14 days after immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg), FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30% dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity of the initial disease and suppressed relapses. FK1706 did not significantly alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity of the initial episode of EAE but did not alter relapses. In the thoracic spinal cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P < 0.001) reduced the extent of damage in the dorsal, lateral, and ventral white matter by a mean of up to ...Continue Reading

References

May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D A FrumanS J Burakoff
Apr 1, 1992·Immunology Today·S L Schreiber, G R Crabtree
Jan 1, 1992·Annual Review of Immunology·N H Sigal, F J Dumont
Jan 1, 1988·International Journal of Immunopharmacology·N InamuraM Kohsaka
Oct 28, 1989·Lancet·T E StarzlA Jain
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·W E LyonsS H Snyder
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E S AlnemriG Litwack
Dec 1, 1995·Brain : a Journal of Neurology·M FilippiD H Miller
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·J P SteinerP D Suzdak
Feb 1, 1997·Journal of Autoimmunity·H YoshikawaM Takamori
Nov 5, 1997·Experimental Neurology·B G GoldD M Armistead
Jan 29, 1998·The New England Journal of Medicine·B D TrappL Bö
Sep 5, 1998·Neuron·S H SnyderP E Burnett
Apr 28, 1999·Lancet·J M DubernardN S Hakim
Jun 8, 1999·Plastic and Reconstructive Surgery·V B Doolabh, S E Mackinnon
Jun 17, 1999·Trends in Neurosciences·M SchwartzI R Cohen
Jul 30, 1999·Journal of Neuroimmunology·B D TrappA Chang
Aug 26, 1999·Drug Metabolism Reviews·B G Gold
Sep 28, 1999·Current Opinion in Neurology·B D TrappR Rudick
Apr 6, 2000·The Journal of Spinal Cord Medicine·M S Wang, B G Gold
Aug 19, 2000·The New England Journal of Medicine·J W JonesW C Breidenbach
Feb 15, 2001·Experimental Neurology·M E EmborgJ H Kordower
Jul 18, 2001·Annals of Neurology·X GuoT M Dawson
Nov 24, 2001·Journal of the Neurological Sciences·H NemotoM Kinoshita

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Citations

Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joseph P SteinerAvindra Nath
Aug 21, 2013·CNS Drugs·Amir-Hadi MaghziEmmanuelle Waubant
Apr 12, 2013·Future Medicinal Chemistry·Alejandra G ErlejmanMario D Galigniana
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael ForteDennis Bourdette
Sep 12, 2012·Multiple Sclerosis International·F JacquesF Grand'maison
Dec 15, 2015·Neurologia i neurochirurgia polska·Dorota Kozielewicz, Małgorzata Pawłowska
Mar 30, 2011·FEBS Letters·Djordje MiljkovićMarija Mostarica Stojković
Apr 26, 2007·The American Journal of Pathology·Tanuja ChitnisSamia J Khoury
Aug 11, 2006·Journal of Neurochemistry·Chunhe WangHalina Offner
Jul 23, 2008·Experimental Dermatology·Yujiro TakaeMasayuki Amagai
Aug 1, 2015·Annals of Neurology·Wendy K RobertsRobert B Darnell
Oct 4, 2005·Journal of Neuroimmunology·Kandace K FlemingJanet G Marquis
Jun 6, 2013·Journal of the Neurological Sciences·Hans Lassmann
Sep 2, 2008·Expert Review of Neurotherapeutics·Albert Lo
Mar 5, 2011·Multiple Sclerosis : Clinical and Laboratory Research·David BakerSandra Amor
May 14, 2005·Current Opinion in Neurology·Catherine LubetzkiBruno Stankoff
Oct 1, 2013·Behavioural Pharmacology·Rimpi B AroraRahul R Deshmukh
Apr 20, 2011·The Journal of Physical Chemistry. B·Marco BizzarriPiero Procacci

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