title: Poly(ADP-ribose) polymerase 2 contributes to neuroinflammation and neurological dysfunction in mouse experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by entry of activated T cells and antigen presenting cells into the central nervous system and subsequent autoimmune destruction of nerve myelin. Previous studies revealed that non-selective inhibition of poly(ADP-ribose) polymerases (PARPs) 1 and 2 protect against neuroinflammation and motor dysfunction associated with EAE, but the role of the PARP-2 isoform has not yet been investigated selectively.
  
  
  RESULTS
  EAE was induced in mice lacking PARP-2, and neurological EAE signs, blood-spine barrier (BSB) permeability, demyelination and inflammatory infiltration were monitored for 35 days after immunization. Mice lacking PARP-2 exhibited significantly reduced overall disease burden and peak neurological dysfunction. PARP-2 deletion also significantly delayed EAE onset and reduced BSB permeability, demyelination and central nervous system (CNS) markers of proinflammatory Th1 and Th17 T helper lymphocytes.
  
  
  CONCLUSIONS
  This study represents the first description of a significant role for PARP-2 in neuroinflammation and neurological dysfunction in EAE.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Kamboj
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cossoy
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Stobart
authors.forename: Brian A
authors.initials: BA
authors.lastname: Dolhun
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Kauppinen
authors.forename: Gilbert
authors.initials: G
authors.lastname: de Murcia
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Anderson
mesh_terms: D000818:Animals; D049428:Blood-Nerve Barrier / Q000502:physiology; D003711:Demyelinating Diseases / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology
chemical_list: D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse