Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice.
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.
Schroeter
Michael
M
Department of Neurology, Heinrich Heine University Düsseldorf, Germany.
Zickler
Philipp
P
Denhardt
David T
DT
Hartung
Hans-Peter
HP
Jander
Sebastian
S
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*
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