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首页> 外文期刊>Neural regeneration research >Acute effects of human protein S administration after traumatic brain injury in mice
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Acute effects of human protein S administration after traumatic brain injury in mice

机译：小鼠创伤性脑损伤后人类蛋白质施用的急性作用

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Despite years of effort, no effective acute phase treatment has been discovered for traumatic brain injury. One impediment to successful drug development is entangled secondary injury pathways. Here we show that protein S, a natural multifunctional protein that regulates coagulation, inflammation, and apoptosis, is able to reduce the extent of multiple secondary injuries in traumatic brain injury, and therefore improve prognosis. Mice subjected to controlled cortical impact were treated acutely (10–15 minutes post-injury) with a single dose of either protein S (1 mg/kg) or vehicle phosphate buffered saline via intravenous injection. At 24 hours post-injury, compared to the non-treated group, the protein S treated group showed substantial improvement of edema and fine motor coordination, as well as mitigation of progressive tissue loss. Immunohistochemistry and western blot targeting caspase-3, B-cell lymphoma 2 (Bcl-2) along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that apoptosis was suppressed in treated animals. Immunohistochemistry targeting CD11b showed limited leukocyte infiltration in the protein S-treated group. Moreover, protein S treatment increased the ipsilesional expression of aquaporin-4, which may be the underlying mechanism of its function in reducing edema. These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis. Animal Use Protocols (AUPs) were approved by the University Committee on Animal Resources (UCAR) of University of Rochester Medical Center (approval No. UCAR-2008-102R) on November 12, 2013.
机译：尽管有多少数努力，但没有发现有效的急性期治疗用于创伤性脑损伤。成功的药物发展的一个障碍是纠缠的二次伤害途径。在这里，我们表明蛋白质S，调节凝血，炎症和凋亡的天然多功能蛋白质，能够降低创伤性脑损伤中多次累伤的程度，从而改善预后。经过受控皮质冲击的小鼠通过静脉内注射用单剂量的蛋白质S（1mg / kg）或磷酸磷酸盐缓冲盐处理急性（损伤后损伤后损伤后损伤后10-15分钟）。损伤后24小时，与未治疗的组相比，蛋白质的治疗组显示水肿和精细电机协调的显着提高，以及缓解渐进组织丧失。免疫组织化学和蛋白质印迹靶向Caspase-3，B细胞淋巴瘤2（Bcl-2）以及末端脱氧核苷酸转移酶DUTP缺口末端标记（TUNEL）测定显示，在处理的动物中抑制了细胞凋亡。免疫组织化学靶向CD11b在蛋白质处理组中显示了有限的白细胞浸润。此外，蛋白质治疗增加了Aquaporin-4的Ipsilesional表达，这可能是其在减少水肿中的功能的潜在机制。这些结果表明，受控皮质冲击后立即静脉内蛋白质治疗有利于创伤性脑损伤预后。 2013年11月12日，罗切斯特医疗中心大学动物资源（UCAR）大学委员会批准了动物使用议定书（AUP）批准了（批准号UCAR-2008-102R）。

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