title: Niaspan treatment improves neurological functional recovery in experimental autoimmune encephalomyelitis mice.
abstract: We investigated the treatment of experimental autoimmune encephalomyelitis (EAE) in mice with Niaspan, an agent used to elevate high-density lipoprotein (HDL). EAE mice were treated with Niaspan starting on the immunization or clinical onset day. Neurological functional recovery was significantly increased in the Niaspan treated mice (100 mg/kgbw) compared to the controls. Inflammatory infiltrates were significantly reduced in the Niaspan treatment group compared to the EAE controls. HDL level, intact myelin area, newly formed oligodendrocytes, regenerating axons, gene and protein levels of sonic hedgehog (Shh)/Gli1 were significantly increased in the Niaspan treated mice compared to EAE controls. These data indicate that Niaspan treatment improved functional recovery after EAE, possibly, via reducing inflammatory infiltrates and demyelination areas, and stimulating oligodendrogenesis and axonal regeneration. Niaspan-mediated activation of Shh/Gli1 pathway may promote functional recovery post-EAE.
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Stanton B
authors.initials: SB
authors.lastname: Elias
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D008076:Cholesterol, HDL / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000009:adverse effects; D009416:Nerve Regeneration / Q000187:drug effects; D009525:Niacin / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D008076:Cholesterol, HDL; D053823:Hedgehog Proteins; D018991:Myelin Proteolipid Protein; C465570:Shh protein, mouse; D014803:Vitamin B Complex; D009525:Niacin
references.citation: Development. 1999 Jun;126(11):2419-29
references.pmid: 10226001
references.citation: J Neuropathol Exp Neurol. 1993 Jan;52(1):55-63
references.pmid: 8381162
references.citation: Ann N Y Acad Sci. 1988;540:712-4
references.pmid: 2462842
references.citation: Lab Invest. 1991 Mar;64(3):358-70
references.pmid: 2002654
references.citation: Mol Cell Neurosci. 2007 Nov;36(3):355-68
references.pmid: 17826177
references.citation: Am J Cardiol. 1998 Dec 17;82(12A):29U-34U;  discussion 39U-41U
references.pmid: 9915660
references.citation: J Neurol Neurosurg Psychiatry. 2003 Jun;74(6):695-7
references.pmid: 12754330
references.citation: J Biol Chem. 2007 Nov 2;282(44):32462-70
references.pmid: 17804404
references.citation: J Neurotrauma. 1992 Mar;9 Suppl 1:S93-103
references.pmid: 1588636
references.citation: Curr Med Res Opin. 2006 Feb;22(2):417-25
references.pmid: 16466614
references.citation: J Neurosci Res. 2008 May 15;86(7):1501-10
references.pmid: 18214988
references.citation: Mult Scler. 2003 Aug;9(4):362-71
references.pmid: 12926841
references.citation: J Neurosci Res. 2001 Nov 15;66(4):691-7
references.pmid: 11746389
references.citation: Int J Biochem Cell Biol. 1998 Mar;30(3):407-15
references.pmid: 9611781
references.citation: Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1724-31
references.pmid: 12969988
references.citation: Glia. 2002 Oct;40(1):55-64
references.pmid: 12237843
references.citation: Neuron. 1997 Jul;19(1):197-203
references.pmid: 9247275
references.citation: Nat Rev Neurosci. 2002 Apr;3(4):291-301
references.pmid: 11967559
references.citation: J Neurosci. 2004 May 5;24(18):4432-43
references.pmid: 15128857
references.citation: Pathol Biol (Paris). 2000 Feb;48(1):80-6
references.pmid: 10729915
references.citation: Nature. 2005 Oct 6;437(7060):894-7
references.pmid: 16208373
references.citation: Nat Rev Cancer. 2002 May;2(5):361-72
references.pmid: 12044012
references.citation: Development. 2001 Feb;128(4):527-40
references.pmid: 11171336
references.citation: Glia. 2005 Oct;52(1):1-15
references.pmid: 15892129
references.citation: Development. 2007 Jan;134(2):285-93
references.pmid: 17166924
references.citation: Glia. 2004 Apr 15;46(2):207-17
references.pmid: 15042587
references.citation: Mol Cell Neurosci. 2002 Mar;19(3):320-32
references.pmid: 11906206
references.citation: Lab Invest. 1981 Dec;45(6):534-46
references.pmid: 7321526
references.citation: Atherosclerosis. 1978 Dec;31(4):465-71
references.pmid: 215176
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13466-71
references.pmid: 15353595
references.citation: Nature. 1983 Jun 2-8;303(5916):390-6
references.pmid: 6304520
references.citation: Am J Cardiol. 1998 Dec 17;82(12A):74U-81U;  discussion 85U-86U
references.pmid: 9915666
references.citation: Glia. 1996 May;17(1):39-51
references.pmid: 8723841
references.citation: J Neurosci Res. 1995 Apr 1;40(5):680-93
references.pmid: 7541477
references.citation: Metabolism. 1998 Sep;47(9):1097-104
references.pmid: 9751239
references.citation: J Neurochem. 2007 Apr;101(2):298-312
references.pmid: 17402967
references.citation: Neurosci Lett. 1992 Feb 3;135(2):219-23
references.pmid: 1625798
references.citation: Brain. 2006 Aug;129(Pt 8):1953-71
references.pmid: 16632554
references.citation: J Neuropathol Exp Neurol. 2005 May;64(5):404-11
references.pmid: 15892298
references.citation: Am J Cardiol. 1998 Sep 15;82(6):737-43
references.pmid: 9761083
references.citation: EMBO J. 2004 Nov 10;23(22):4495-505
references.pmid: 15496983
references.citation: Circ Res. 2004 Oct 15;95(8):764-72
references.pmid: 15486323
references.citation: Int J Clin Pract. 2004 Jul;58(7):706-13
references.pmid: 15311728
references.citation: J Nutr Sci Vitaminol (Tokyo). 1982 Oct;28(5):491-500
references.pmid: 7161647
references.citation: Purinergic Signal. 2008 Mar;4(1):61-71
references.pmid: 18368534
references.citation: J Biol Chem. 2000 Jun 30;275(26):19883-90
references.pmid: 10867025
references.citation: Glia. 1998 Feb;22(2):161-70
references.pmid: 9537836
references.citation: Nature. 1986 Feb 6-12;319(6053):499-502
references.pmid: 3945333
references.citation: Brain. 1994 Jun;117 ( Pt 3):563-78
references.pmid: 8032866
references.citation: J Clin Invest. 1989 Mar;83(3):1015-31
references.pmid: 2493483
references.citation: Expert Opin Pharmacother. 2004 Jun;5(6):1385-98
references.pmid: 15163282
references.citation: Neth J Med. 2004 Jul-Aug;62(7):229-34
references.pmid: 15554597
references.citation: Nat Med. 1999 Feb;5(2):170-5
references.pmid: 9930864
references.citation: J Neurosci Res. 2001 Jan 15;63(2):124-35
references.pmid: 11169622
references.citation: Ann Neurol. 2000 Jun;47(6):707-17
references.pmid: 10852536
references.citation: Dev Neurosci. 2001;23(6):452-63
references.pmid: 11872946
references.citation: J Neurosci. 2000 Sep 1;20(17):6404-12
references.pmid: 10964946
references.citation: Dev Neurosci. 2007;29(6):413-26
references.pmid: 17119318
references.citation: Am J Pathol. 1979 Jun;95(3):683-96
references.pmid: 453329
references.citation: J Neurosci Res. 2006 Mar;83(4):606-18
references.pmid: 16435391
references.citation: Am J Cardiol. 1998 Dec 17;82(12A):35U-38U;  discussion 39U-41U
references.pmid: 9915661
references.citation: J Neurochem. 2001 Jan;76(2):498-508
references.pmid: 11208913
references.citation: Dev Neurosci. 1995;17(3):160-70
references.pmid: 8549427
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Neurosci Res. 1999 Sep 1;57(5):633-42
references.pmid: 10462687
references.citation: J Neurochem. 1993 Feb;60(2):577-87
references.pmid: 7678286
references.citation: Ann Neurol. 2007 Jul;62(1):49-58
references.pmid: 17557352
references.citation: Brain. 2002 Oct;125(Pt 10):2202-12
references.pmid: 12244078
references.citation: Lab Invest. 1989 Nov;61(5):489-503
references.pmid: 2811298
references.citation: Genes Dev. 2001 Dec 1;15(23):3059-87
references.pmid: 11731473
references.citation: J Cell Biol. 1989 Nov;109(5):2405-16
references.pmid: 2553746
references.citation: Brain Res. 2005 Feb 9;1034(1-2):34-9
references.pmid: 15713257
references.citation: Trends Neurosci. 2002 Feb;25(2):89-96
references.pmid: 11814561
references.citation: Exp Neurol. 2005 Sep;195(1):16-26
references.pmid: 15904921
references.citation: Nature. 1984 Mar 15-21;308(5956):274-5
references.pmid: 6700730