Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats.
Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats.
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DOI：
10.1097/ccm.0b013e3181c027ae
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发表时间：
2010-02
影响因子：
8.8
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Suzuki H;Ayer R;Sugawara T;Chen W;Sozen T;Hasegawa Y;Kanamaru K;Zhang JH
Accumulated evidence suggests that the primary cause of poor outcome after subarachnoid hemorrhage (SAH) is not only cerebral arterial narrowing, but also early brain injury (EBI). Our objective was to determine the effect of recombinant osteopontin (r-OPN), a pleiotropic extracellular matrix glycoprotein, on post-SAH EBI in rats. Controlled in vivo laboratory study. Animal research laboratory. One hundred seventy-seven male adult Sprague-Dawley rats, 300–370g. The endovascular perforation model of SAH was produced. SAH or sham-operated rats were treated with an equal volume (1μL) of pre-SAH intracerebroventricular administration of two dosages (0.02 and 0.1μg) of r-OPN, albumin or vehicle. Body weight, neurological scores, brain edema and blood-brain barrier (BBB) disruption were evaluated, and Western blot analyses were performed to determine the effect of r-OPN on matrix metalloproteinase (MMP)-9, substrates of MMP-9 (zona occludens [ZO]-1, laminin), tissue inhibitor of MMP (TIMP)-1, inflammation (interleukin-1β), and nuclear factor (NF)-κ B signaling pathways. Treatment with r-OPN prevented a significant loss in body weight, neurological impairment, brain edema, and BBB disruption after SAH. These effects were associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, the maintenance of TIMP-1, and the consequent preservation of the cerebral microvessel basal lamina protein laminin, and the tight junction protein ZO-1. These results demonstrate that r-OPN treatment is effective for post-SAH EBI.
