Schroeter Michael, Zickler Philipp, Denhardt David T, Hartung Hans-Peter, Jander Sebastian
Department of Neurology, Heinrich Heine University Düsseldorf, Germany.
Brain. 2006 Jun;129(Pt 6):1426-37. doi: 10.1093/brain/awl094. Epub 2006 Apr 24.
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.
炎症会加重中风和神经退行性变所导致的脑损伤。骨桥蛋白（OPN）是一种细胞因子样糖蛋白，可与多种整合素及CD44变体结合。OPN在自身免疫性疾病中发挥促炎作用，但也具有细胞保护特性并参与伤口愈合。在本研究中，我们利用OPN基因敲除（KO）小鼠，在皮质中风模型中探讨了OPN在缺血性脑损伤中的作用。与野生型动物相比，OPN KO小鼠在原发性损伤部位的梗死发展未发生改变，但同侧丘脑的逆行性变性显著增加。OPN缺陷小鼠的丘脑神经退行性变与明显的小胶质细胞激活及炎症基因表达有关，并且可通过诱导型一氧化氮合酶（iNOS）的药理学阻断而减轻。因此，OPN缺陷小鼠中延迟的神经退行性变至少部分归因于通过iNOS途径过度释放一氧化氮。OPN的神经保护和抗炎作用可能与多种神经系统疾病状况相关。
