Elucidation of pathogenesis and new treatment for brain injury after subarachnoid hemorrhage

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Subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) potentially contributes to poor outcome, one of whose key pathologic manifestation is the breakdown of the blood-brain barrier (BBB). We determined the role of osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein (matricellular protein [MCP]), in the post-SAH BBB disruption in rats. The OPN levels in the brain were significantly induced and peaked at 72 hours after SAH, in the recovery phase of EBI. OPN siRNA significantly blocked the endogenous OPN induction and aggravated neurological impairment and BBB disruption at 72 hours after SAH. Pre-SAH administration of recombinant OPN (r-OPN)significantly prevented a loss in body weight, neurological impairment, brain edema and BBB disruption compared with the control rats. Treatment with r-OPN was associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, and the consequent preservation of cerebral microvessel basal lamina proteins and tight junction proteins.These findings suggest the protective effects of OPN against BBB disruption after SAH.In addition, we obtained new findings, suggesting that tenascin-C, another MCP, causes brain injury after SAH.