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Currently, clinical treatments for neurological dysfunction of acute brain injury have not been satisfactory. Osteopontin (OPN) is a complex adhesion protein and cytokine that interacts with multiple receptors including integrins and CD44 variants, exhibiting mostly neuroprotective roles and showing therapeutic potential for acute brain injury. OPN\u2010induced tissue remodelling and functional repair mainly rely on its positive roles in the coordination of pro\u2010inflammatory and anti\u2010inflammatory responses, blood\u2010brain barrier maintenance and anti\u2010apoptotic actions, as well as other mechanisms such as affecting the chemotaxis and proliferation of nerve cells. The blood OPN strongly parallel with the OPN induced in the brain and can be used as a novel biomarker of the susceptibility, severity and outcome of acute brain injury. 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