title: Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice.
abstract: Inflammation aggravates brain injury caused by stroke and neurodegeneration. Osteopontin (OPN) is a cytokine-like glycoprotein that binds to various integrins and CD44 variants. OPN exerts proinflammatory effects in autoimmune conditions but also has cytoprotective properties and participates in wound healing. In this study, we addressed the role of OPN in ischaemic brain injury using OPN knock-out (KO) mice in models of cortical stroke. Compared with wild-type animals, OPN KO mice exhibited unaltered infarct development at the primary injury site but greatly increased retrograde degeneration of the ipsilateral thalamus. Thalamic neurodegeneration in OPN-deficient mice was associated with pronounced microglia activation and inflammatory gene expression and could be attenuated via pharmacological blockade of the inducible nitric oxide synthase (iNOS). Therefore, delayed neurodegeneration in OPN-deficient mice was at least partly due to an excessive release of nitric oxide via the iNOS pathway. Neuroprotective and anti-inflammatory effects of OPN may be relevant for a variety of neurological disease conditions.
authors.affiliation: Department of Neurology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.forename: Philipp
authors.initials: P
authors.lastname: Zickler
authors.forename: David T
authors.initials: DT
authors.lastname: Denhardt
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jander
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology; D053495:Osteopontin; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II