Effects of Recombinant Osteopontin on Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Rats

Objects: We determined effects of recombinant OPN (r-OPN), a pleiotropic extracellular matrix protein, on blood-brain barrier (BBB) disruption and matrix metalloproteinase (MMP)-9 activation after subarachnoid hemorrhage (SAH) in rats. Methods: The endovascular perforation model of SAH was used. SAH or sham-operated rats were treated with pre-SAH intracerebroventricular administration of two dosages of r-OPN, r-OPN + GRGDSP (an L-arginyl-glycyl-L-aspartate-dependent integrin receptor antagonist), albumin or vehicle. Neurological impairments, brain edema and BBB disruption were evaluated, and Western blot analyses were performed in the brain at 24 h after SAH. Results: r-OPN significantly prevented brain edema and BBB disruption compared with the control rats, associated with the suppression of nuclear factor-κB and mitogen-activated protein kinase pathways, leading to MMP-9 inactivation. These effects were blocked by GRGDSP. Conclusions: L-arginyl-glycyl-L-aspartate-dependent integrin receptor-mediated multiple signaling pathways may be involved in the protective effects of r-OPN against BBB disruption after SAH.