title: Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by infiltration of T cells into the central nervous system (CNS) after compromise of the blood-brain barrier. A model used to mimic the disease in mice is experimental autoimmune encephalomyelitis (EAE). In this report, we examine the clinical and histopathological course of EAE in eNOS-deficient (eNOS-/-) mice to determine the role of nitric oxide (NO) derived from this enzyme in the disease progression. We find that eNOS-/- mice exhibit a delayed onset of EAE that correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS underlies the T cell infiltration into the CNS. However, the eNOS-/- mice also eventually exhibit more severe EAE and delayed recovery, indicating that NO undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset, and the other neuroprotective that promotes recovery from disease exacerbation events.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794-8651, USA.
authors.forename: Muzhou
authors.initials: M
authors.lastname: Wu
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009186:Myelin Sheath / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse