Advancement of therapies for neuroprotection in multiple sclerosis

References

• Frohman EM, Stuve O, Havrdova E et al. Therapeutic considerations for disease progression in multiple sclerosis: evidence, experience, and future expectations. Arch. Neurol.62(10), 1519–1530 (2005).
   PubMedGoogle Scholar
• Frohman EM, Filippi M, Stuve O et al. Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions. Arch. Neurol.62(9), 1345–1356 (2005).
   PubMedGoogle Scholar
• De Stefano N, Bartolozzi ML, Guidi L, Stromillo ML, Federico A. Magnetic resonance spectroscopy as a measure of brain damage in multiple sclerosis. J. Neurol. Sci.233(1–2), 203–208 (2005).
   PubMed Web of Science ®Google Scholar
• Fisher E, Rudick RA, Simon JH et al. Eight-year follow-up study of brain atrophy in patients with MS. Neurology59(9), 1412–1420 (2002).
   PubMed Web of Science ®Google Scholar
• Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol.5(4), 343–354 (2006).
   PubMed Web of Science ®Google Scholar
• Filippini G, Munari L, Incorvaia B et al. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet361(9357), 545–552 (2003).
   PubMed Web of Science ®Google Scholar
• Lassmann H. Multiple sclerosis: is there neurodegeneration independent from inflammation? J. Neurol. Sci.259(1–2), 3–6 (2007).
   PubMed Web of Science ®Google Scholar
• Koch M, Mostert J, Heersema D, De Keyser J. Progression in multiple sclerosis: further evidence of an age dependent process. J. Neurol. Sci.255(1–2), 35–41 (2007).
   PubMed Web of Science ®Google Scholar
• Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult. Scler.9(4), 323–331 (2003).
   PubMed Web of Science ®Google Scholar
• Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol.47(6), 707–717 (2000).
   PubMed Web of Science ®Google Scholar
• Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med.338(5), 278–285 (1998).
   PubMed Web of Science ®Google Scholar
• Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH. Brain atrophy in clinically early relapsing–remitting multiple sclerosis. Brain125(Pt 2), 327–337 (2002).
   PubMed Web of Science ®Google Scholar
• Coles AJ, Wing MG, Molyneux P et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann. Neurol.46(3), 296–304 (1999).
   PubMed Web of Science ®Google Scholar
• Parry A, Corkill R, Blamire AM et al. β-interferon treatment does not always slow the progression of axonal injury in multiple sclerosis. J. Neurol.250(2), 171–178 (2003).
   PubMed Web of Science ®Google Scholar
• Palace J. Inflammation versus neurodegeneration: consequences for treatment. J. Neurol. Sci.259(1–2), 46–49 (2007).
   PubMed Web of Science ®Google Scholar
• Hardmeier M, Wagenpfeil S, Freitag P et al. Rate of brain atrophy in relapsing MS decreases during treatment with IFNβ-1a. Neurology64(2), 236–240 (2005).
   PubMed Web of Science ®Google Scholar
• Hickman SJ, Kapoor R, Jones SJ, Altmann DR, Plant GT, Miller DH. Corticosteroids do not prevent optic nerve atrophy following optic neuritis. J. Neurol. Neurosurg. Psychiatry74(8), 1139–1141 (2003).
   PubMed Web of Science ®Google Scholar
• O’Connor P. Natalizumab and the role of α 4-integrin antagonism in the treatment of multiple sclerosis. Expert Opin. Biol. Ther.7(1), 123–136 (2007).
   PubMed Web of Science ®Google Scholar
• Bradl M, Hohlfeld R. Molecular pathogenesis of neuroinflammation. J. Neurol. Neurosurg. Psychiatry74(10), 1364–1370 (2003).
   PubMed Web of Science ®Google Scholar
• Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ. Interferon β-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology60(1), 44–51 (2003).
   PubMed Web of Science ®Google Scholar
• Montalban X. Overview of European pilot study of interferon β-Ib in primary progressive multiple sclerosis. Mult. Scler.10Suppl. 1, S62; discussion 62–64 (2004).
   Google Scholar
• Wolinsky JS. The PROMiSe trial: baseline data review and progress report. Mult. Scler.40(Suppl. 1), S65–S71 discussion S71–S62 (2004).
   Google Scholar
• Ramsaransing G, Zwanikken C, De Keyser J. Worsening of symptoms of multiple sclerosis associated with carbamazepine. BMJ320(7242), 1113 (2000).
   PubMed Web of Science ®Google Scholar
• Poliak S, Peles E. The local differentiation of myelinated axons at nodes of Ranvier. Nat. Rev. Neurosci.4(12), 968–980 (2003).
   PubMed Web of Science ®Google Scholar
• Stys PK. General mechanisms of axonal damage and its prevention. J. Neurol. Sci.233(1–2), 3–13 (2005).
   PubMed Web of Science ®Google Scholar
• Smith KJ, Lassmann H. The role of nitric oxide in multiple sclerosis. Lancet Neurol.1(4), 232–241 (2002).
   PubMed Web of Science ®Google Scholar
• Brown GC, Borutaite V. Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radic. Biol. Med.33(11), 1440–1450 (2002).
   PubMed Web of Science ®Google Scholar
• Lassmann H. Hypoxia-like tissue injury as a component of multiple sclerosis lesions. J. Neurol. Sci.206(2), 187–191 (2003).
   PubMed Web of Science ®Google Scholar
• Stys PK, Waxman SG, Ransom BR. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na+-Ca2+ exchanger. J. Neurosci.12(2), 430–439 (1992).
   PubMed Web of Science ®Google Scholar
• Craner MJ, Hains BC, Lo AC, Black JA, Waxman SG. Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain127(Pt 2), 294–303 (2004).
   PubMed Web of Science ®Google Scholar
• Levy LM, Warr O, Attwell D. Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J. Neurosci.18(23), 9620–9628 (1998).
   PubMed Web of Science ®Google Scholar
• Micu I, Jiang Q, Coderre E et al. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature439(7079), 988–992 (2006).
   PubMed Web of Science ®Google Scholar
• Zerangue N, Kavanaugh MP. Flux coupling in a neuronal glutamate transporter. Nature383(6601), 634–637 (1996).
   PubMed Web of Science ®Google Scholar
• Ragsdale DS, Avoli M. Sodium channels as molecular targets for antiepileptic drugs. Brain Res. Rev.26(1), 16–28 (1998).
   PubMed Web of Science ®Google Scholar
• Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc. Natl. Acad. Sci. USA93(17), 9270–9275 (1996).
   PubMed Web of Science ®Google Scholar
• Schwarz JR, Grigat G. Phenytoin and carbamazepine: potential- and frequency-dependent block of Na currents in mammalian myelinated nerve fibers. Epilepsia30(3), 286–294 (1989).
   PubMed Web of Science ®Google Scholar
• Fern R, Ransom BR, Stys PK, Waxman SG. Pharmacological protection of CNS white matter during anoxia: actions of phenytoin, carbamazepine and diazepam. J. Pharmacol. Exp. Ther.266(3), 1549–1555 (1993).
   PubMed Web of Science ®Google Scholar
• Lo AC, Black JA, Waxman SG. Neuroprotection of axons with phenytoin in experimental allergic encephalomyelitis. Neuroreport13(15), 1909–1912 (2002).
   PubMed Web of Science ®Google Scholar
• Lo AC, Saab CY, Black JA, Waxman SG. Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. J. Neurophysiol.90(5), 3566–3571 (2003).
   PubMed Web of Science ®Google Scholar
• Black JA, Liu S, Hains BC, Saab CY, Waxman SG. Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE. Brain129(Pt 12), 3196–3208 (2006).
   PubMed Web of Science ®Google Scholar
• Kuo CC. A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol. Pharmacol.54(4), 712–721 (1998).
   PubMed Web of Science ®Google Scholar
• Lang DG, Wang CM, Cooper BR. Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells. J. Pharmacol. Exp. Ther.266(2), 829–835 (1993).
   PubMed Web of Science ®Google Scholar
• Calabresi P, Centonze D, Marfia GA, Pisani A, Bernardi G. An in vitro electrophysiological study on the effects of phenytoin, lamotrigine and gabapentin on striatal neurons. Br. J. Pharmacol.126(3), 689–696 (1999).
   PubMed Web of Science ®Google Scholar
• Stefani A, Spadoni F, Bernardi G. Differential inhibition by riluzole, lamotrigine, and phenytoin of sodium and calcium currents in cortical neurons: implications for neuroprotective strategies. Exp. Neurol.147(1), 115–122 (1997).
   PubMed Web of Science ®Google Scholar
• Wang SJ, Huang CC, Hsu KS, Tsai JJ, Gean PW. Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones. Neuroreport7(18), 3037–3040 (1996).
   PubMed Web of Science ®Google Scholar
• Smith T, Groom A, Zhu B, Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat. Med.6(1), 62–66 (2000).
   PubMed Web of Science ®Google Scholar
• Lagrue E, Chalon S, Bodard S, Saliba E, Gressens P, Castelnau P. Lamotrigine is neuroprotective in the energy deficiency model of MPTP intoxicated mice. Pediatr. Res.62(1), 14–19 (2007).
   PubMed Web of Science ®Google Scholar
• Garthwaite G, Brown G, Batchelor AM, Goodwin DA, Garthwaite J. Mechanisms of ischaemic damage to central white matter axons: a quantitative histological analysis using rat optic nerve. Neuroscience94(4), 1219–1230 (1999).
   PubMed Web of Science ®Google Scholar
• Bechtold DA, Miller SJ, Dawson AC et al. Axonal protection achieved in a model of multiple sclerosis using lamotrigine. J. Neurol.253(12), 1542–1551 (2006).
   PubMed Web of Science ®Google Scholar
• Kapoor R. Neuroprotection in multiple sclerosis: therapeutic strategies and clinical trial design. Curr. Opin. Neurol.19(3), 255–259 (2006).
   PubMed Web of Science ®Google Scholar
• Craner MJ, Damarjian TG, Liu S et al. Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia49(2), 220–229 (2005).
   PubMed Web of Science ®Google Scholar
• Okamoto Y, Shimizu K, Tamura K et al. Effects of phenytoin on cell-mediated immunity. Cancer Immunol. Immunother.26(2), 176–179 (1988).
   PubMed Web of Science ®Google Scholar
• Black JA, Liu S, Carrithers M, Carrithers LM, Waxman SG. Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine. Ann. Neurol.62(1), 21–33 (2007).
   PubMed Web of Science ®Google Scholar
• Makowska A, Bechtold D, Sajic M, Gregson N, Hughes R, Smith S. Sodium channel blocking agents affect T cell activation. Presented at: International Society of Neuroimmunology: Seventh International Congress. J. Neuroimmunol. Venice, Italy, 88 (2004).
   Google Scholar
• Waxman SG. Mechanisms of disease: sodium channels and neuroprotection in multiple sclerosis – current status. Nat. Clin. Pract. Neurol.4(3), 159–169 (2008).
   PubMedGoogle Scholar
• Sun GC, Werkman TR, Battefeld A, Clare JJ, Wadman WJ. Carbamazepine and topiramate modulation of transient and persistent sodium currents studied in HEK293 cells expressing the Nav1.3 α-subunit. Epilepsia48(4), 774–782 (2007).
   PubMed Web of Science ®Google Scholar
• Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med.330(9), 613–622 (1994).
   PubMed Web of Science ®Google Scholar
• Rothman SM, Olney JW. Excitotoxicity and the NMDA receptor – still lethal after eight years. Trends Neurosci.18(2), 57–58 (1995).
   PubMed Web of Science ®Google Scholar
• Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain128(Pt 5), 1016–1025 (2005).
   PubMed Web of Science ®Google Scholar
• Stover JF, Pleines UE, Morganti-Kossmann MC, Kossmann T, Lowitzsch K, Kempski OS. Neurotransmitters in cerebrospinal fluid reflect pathological activity. Eur. J. Clin. Invest.27(12), 1038–1043 (1997).
   PubMed Web of Science ®Google Scholar
• Sarchielli P, Greco L, Floridi A, Gallai V. Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid. Arch. Neurol.60(8), 1082–1088 (2003).
   PubMedGoogle Scholar
• Pitt D, Werner P, Raine CS. Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med.6(1), 67–70 (2000).
   PubMed Web of Science ®Google Scholar
• Geurts JJ, Wolswijk G, Bo L et al. Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain126(Pt 8), 1755–1766 (2003).
   PubMed Web of Science ®Google Scholar
• Stys PK, Lipton SA. White matter NMDA receptors: an unexpected new therapeutic target? Trends Pharmacol. Sci.28(11), 561–566 (2007).
   PubMed Web of Science ®Google Scholar
• Wallstrom E, Diener P, Ljungdahl A, Khademi M, Nilsson CG, Olsson T. Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis. J. Neurol. Sci.137(2), 89–96 (1996).
   PubMed Web of Science ®Google Scholar
• Gilgun-Sherki Y, Panet H, Melamed E, Offen D. Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis. Brain Res.989(2), 196–204 (2003).
   PubMed Web of Science ®Google Scholar
• Kalkers NF, Ameziane N, Bot JC, Minneboo A, Polman CH, Barkhof F. Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype. Arch. Neurol.59(10), 1572–1576 (2002).
   PubMedGoogle Scholar
• Killestein J, Kalkers NF, Polman CH. Glutamate inhibition in MS: the neuroprotective properties of riluzole. J. Neurol. Sci.233(1–2), 113–115 (2005).
   PubMed Web of Science ®Google Scholar
• Kino T, Hatanaka H, Hashimoto M et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J. Antibiot.40(9), 1249–1255 (1987).
   PubMed Web of Science ®Google Scholar
• Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A. FK 506 for liver, kidney, and pancreas transplantation. Lancet2(8670), 1000–1004 (1989).
   PubMed Web of Science ®Google Scholar
• Gold BG, Voda J, Yu X, McKeon G, Bourdette DN. FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis. J. Neurosci. Res.77(3), 367–377 (2004).
   PubMed Web of Science ®Google Scholar
• Gold BG, Zhong YP. FK506 requires stimulation of the extracellular signal-regulated kinase 1/2 and the steroid receptor chaperone protein p23 for neurite elongation. Neurosignals13(3), 122–129 (2004).
   PubMedGoogle Scholar
• Sanchez ER. Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. J. Biol. Chem.265(36), 22067–22070 (1990).
   PubMed Web of Science ®Google Scholar
• Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL. Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science256(5061), 1315–1318 (1992).
   PubMed Web of Science ®Google Scholar
• Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology65(6), 812–819 (2005).
   PubMed Web of Science ®Google Scholar
• Zajicek J, Fox P, Sanders H et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet362(9395), 1517–1526 (2003).
   PubMed Web of Science ®Google Scholar
• Croxford JL, Pryce G, Jackson SJ et al. Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J. Neuroimmunol.193(1–2), 120–129 (2008).
   PubMed Web of Science ®Google Scholar
• Jackson SJ, Baker D, Cuzner ML, Diemel LT. Cannabinoid-mediated neuroprotection following interferon-γ treatment in a three-dimensional mouse brain aggregate cell culture. Eur. J. Neurosci.20(9), 2267–2275 (2004).
   PubMed Web of Science ®Google Scholar
• Bilsland LG, Dick JR, Pryce G et al. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. FASEB J.20(7), 1003–1005 (2006).
   PubMed Web of Science ®Google Scholar
• Zajicek JP, Sanders HP, Wright DE et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J. Neurol. Neurosurg. Psychiatry76(12), 1664–1669 (2005).
   PubMed Web of Science ®Google Scholar
• Docagne F, Mestre L, Loria F, Hernangomez M, Correa F, Guaza C. Therapeutic potential of CB2 targeting in multiple sclerosis. Expert Opin. Ther. Targets12(2), 185–195 (2008).
   PubMed Web of Science ®Google Scholar
• Docagne F, Muneton V, Clemente D et al. Excitotoxicity in a chronic model of multiple sclerosis: neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation. Mol. Cell Neurosci.34(4), 551–561 (2007).
   PubMed Web of Science ®Google Scholar
• Nessler S, Dodel R, Bittner A et al. Effect of minocycline in experimental autoimmune encephalomyelitis. Ann. Neurol.52(5), 689–690; author reply 690 (2002).
   PubMed Web of Science ®Google Scholar
• Popovic N, Schubart A, Goetz BD, Zhang SC, Linington C, Duncan ID. Inhibition of autoimmune encephalomyelitis by a tetracycline. Ann. Neurol.51(2), 215–223 (2002).
   PubMed Web of Science ®Google Scholar
• Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol.3(12), 744–751 (2004).
   PubMed Web of Science ®Google Scholar
• Metz LM, Zhang Y, Yeung M et al. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann. Neurol.55(5), 756 (2004).
   PubMed Web of Science ®Google Scholar
• Zabad RK, Metz LM, Todoruk TR et al. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult. Scler.13(4), 517–526 (2007).
   PubMed Web of Science ®Google Scholar
• Wang J, Wei Q, Wang CY, Hill WD, Hess DC, Dong Z. Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J. Biol. Chem.279(19), 19948–19954 (2004).
   PubMed Web of Science ®Google Scholar
• Zhu S, Stavrovskaya IG, Drozda M et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature417(6884), 74–78 (2002).
   PubMed Web of Science ®Google Scholar
• Gabler WL, Smith J, Tsukuda N. Comparison of doxycycline and a chemically modified tetracycline inhibition of leukocyte functions. Res. Commun. Chem. Pathol. Pharmacol.78(2), 151–160 (1992).
   PubMedGoogle Scholar
• Maier K, Merkler D, Gerber J et al. Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation. Neurobiol. Dis.25(3), 514–525 (2007).
   PubMed Web of Science ®Google Scholar
• Gordon PH, Moore DH, Miller RG et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a Phase III randomised trial. Lancet Neurol.6(12), 1045–1053 (2007).
   PubMed Web of Science ®Google Scholar
• Aktas O, Prozorovski T, Smorodchenko A et al. Green tea epigallocatechin-3-gallate mediates T cellular NF-κB inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J. Immunol.173(9), 5794–5800 (2004).
   PubMed Web of Science ®Google Scholar
• Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis19(10), 1771–1776 (1998).
   PubMed Web of Science ®Google Scholar
• Pisters KM, Newman RA, Coldman B et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J. Clin. Oncol.19(6), 1830–1838 (2001).
   PubMed Web of Science ®Google Scholar
• Brown AM, Tekkok SB, Ransom BR. Glycogen regulation and functional role in mouse white matter. J. Physiol.549>(Pt 2), 501–512 (2003).
   PubMed Web of Science ®Google Scholar
• De Keyser J, Zeinstra E, Mostert J, Wilczak N. β2-adrenoceptor involvement in inflammatory demyelination and axonal degeneration in multiple sclerosis. Trends Pharmacol. Sci.25(2), 67–71 (2004).
   PubMed Web of Science ®Google Scholar
• Kong EK, Peng L, Chen Y, Yu AC, Hertz L. Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration. Neurochem. Res.27(1–2), 113–120 (2002).
   PubMed Web of Science ®Google Scholar
• Mostert JP, Sijens PE, Oudkerk M, De Keyser J. Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis. Neurosci. Lett.402(1–2), 22–24 (2006).
   PubMed Web of Science ®Google Scholar
• Cambray-Deakin M, Pearce B, Morrow C, Murphy S. Effects of neurotransmitters on astrocyte glycogen stores in vitro. J. Neurochem.51(6), 1852–1857 (1988).
   PubMed Web of Science ®Google Scholar
• Mercier G, Lennon AM, Renouf B et al. MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes. J. Mol. Neurosci.24(2), 207–216 (2004).
   PubMed Web of Science ®Google Scholar
• Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H. BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain125(Pt 1), 75–85 (2002).
   PubMed Web of Science ®Google Scholar
• Ehrenreich H, Fischer B, Norra C et al. Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain130(Pt 10), 2577–2588 (2007).
   PubMed Web of Science ®Google Scholar
• Ehrenreich H, Hasselblatt M, Dembowski C et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol. Med.8(8), 495–505 (2002).
   PubMed Web of Science ®Google Scholar
• Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined Phase I and II clinical trial. N. Engl. J. Med.316(2), 73–78 (1987).
   PubMed Web of Science ®Google Scholar
• Sattler MB, Merkler D, Maier K et al. Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis. Cell Death Differ11(Suppl. 2), S181–S192 (2004).
   PubMedGoogle Scholar
• Celik M, Gokmen N, Erbayraktar S et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc. Natl Acad. Sci. USA99(4), 2258–2263 (2002).
   PubMed Web of Science ®Google Scholar
• Keswani SC, Buldanlioglu U, Fischer A et al. A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. Ann. Neurol.56(6), 815–826 (2004).
   PubMed Web of Science ®Google Scholar
• Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T. Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res.609(1–2), 29–35 (1993).
   PubMed Web of Science ®Google Scholar
• Whitacre CC. Sex differences in autoimmune disease. Nat. Immunol.2(9), 777–780 (2001).
   PubMed Web of Science ®Google Scholar
• Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N. Engl. J. Med.339(5), 285–291 (1998).
   PubMed Web of Science ®Google Scholar
• Offner H, Adlard K, Zamora A, Vandenbark AA. Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis. J. Clin. Invest.105(10), 1465–1472 (2000).
   PubMed Web of Science ®Google Scholar
• Offner H, Polanczyk M. A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. Ann. NY Acad. Sci.1089, 343–372 (2006).
   PubMed Web of Science ®Google Scholar
• Bebo BF Jr, Fyfe-Johnson A, Adlard K, Beam AG, Vandenbark AA, Offner H. Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains. J. Immunol.166(3), 2080–2089 (2001).
   PubMed Web of Science ®Google Scholar
• Ito A, Bebo BF Jr, Matejuk A et al. Estrogen treatment down-regulates TNF-α production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J. Immunol.167(1), 542–552 (2001).
   PubMed Web of Science ®Google Scholar
• Tiwari-Woodruff S, Morales LB, Lee R, Voskuhl RR. Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER)α and ERβ ligand treatment. Proc. Natl Acad. Sci. USA104(37), 14813–14818 (2007).
   PubMed Web of Science ®Google Scholar
• Sicotte NL, Liva SM, Klutch R et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann. Neurol.52(4), 421–428 (2002).
   PubMed Web of Science ®Google Scholar
• Sicotte NL, Giesser BS, Tandon V et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch. Neurol.64(5), 683–688 (2007).
   PubMed Web of Science ®Google Scholar
• Czlonkowska A, Ciesielska A, Joniec I. Influence of estrogens on neurodegenerative processes. Med. Sci. Monit.9(10), RA247–RA256 (2003).
   PubMedGoogle Scholar
• McEwen BS. Invited review: estrogens effects on the brain: multiple sites and molecular mechanisms. J. Appl. Physiol.91(6), 2785–2801 (2001).
   PubMed Web of Science ®Google Scholar
• Toran-Allerand CD, Singh M, Setalo G Jr. Novel mechanisms of estrogen action in the brain: new players in an old story. Front. Neuroendocrinol.20(2), 97–121 (1999).
   PubMed Web of Science ®Google Scholar
• Ernfors P. Local and target-derived actions of neurotrophins during peripheral nervous system development. Cell Mol. Life Sci.58(8), 1036–1044 (2001).
   PubMed Web of Science ®Google Scholar
• Teng KK, Hempstead BL. Neurotrophins and their receptors: signaling trios in complex biological systems. Cell Mol. Life Sci.61(1), 35–48 (2004).
   PubMed Web of Science ®Google Scholar
• Giess R, Maurer M, Linker R et al. Association of a null mutation in the CNTF gene with early onset of multiple sclerosis. Arch. Neurol.59(3), 407–409 (2002).
   PubMedGoogle Scholar
• Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H. The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J. Neuroimmunol.107(2), 161–166 (2000).
   PubMed Web of Science ®Google Scholar
• Azoulay D, Urshansky N, Karni A. Low and dysregulated BDNF secretion from immune cells of MS patients is related to reduced neuroprotection. J. Neuroimmunol.195(1–2), 186–193 (2008).
   PubMed Web of Science ®Google Scholar
• Kuhlmann T, Remington L, Cognet I et al. Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis. Am. J. Pathol.169(2), 584–598 (2006).
   PubMed Web of Science ®Google Scholar
• Miller D, Briggs J. Reliability of trans-cervical recovery of placental cells from the lower uterine pole using a minimally invasive procedure. Evidence based on fetal sexing and analysis of recovered cell populations. Early Hum. Dev.47(Suppl.), S99–S102 (1996).
   PubMedGoogle Scholar
• Makar TK, Trisler D, Sura KT, Sultana S, Patel N, Bever CT. Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis. J. Neurol. Sci.270(1–2), 70–76 (2008).
   PubMed Web of Science ®Google Scholar
• Frank JA, Richert N, Lewis B et al. A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients. Mult. Scler.8(1), 24–29 (2002).
   PubMed Web of Science ®Google Scholar
• Lin X, Blumhardt LD, Constantinescu CS. The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study. Acta Neurol. Scandinavica108(6), 401–406 (2003).
   PubMed Web of Science ®Google Scholar
• Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol.5(2), 158–170 (2006).
   PubMed Web of Science ®Google Scholar
• Khan O. Can clinical outcomes be used to detect neuroprotection in multiple sclerosis? Neurology68(22 Suppl. 3), S64–S71; discussion S91–96 (2007).
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Cox JL. Neuroimaging in multiple sclerosis. Int. Rev. Neurobiol.79, 449–474 (2007).
   PubMed Web of Science ®Google Scholar
• Frohman EM, Costello F, Stuve O et al. Modeling axonal degeneration within the anterior visual system: implications for demonstrating neuroprotection in multiple sclerosis. Arch. Neurol.65(1), 26–35 (2008).
   PubMedGoogle Scholar
• Eikelenboom MJ, Petzold A, Lazeron RH et al. Multiple sclerosis: neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology60(2), 219–223 (2003).
   PubMed Web of Science ®Google Scholar