Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury
Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury
复制标题
载脂蛋白 E-模拟 COG1410 可减轻创伤性脑损伤后的急性血管源性水肿
DOI：
10.1089/neu.2015.3887
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发表时间：
2016-01-15
影响因子：
4.2
通讯作者：
Sun, Xiaochuan
中科院分区：
文献类型：
--
作者：
Cao, Fang;Jiang, Yong;Sun, Xiaochuan
创伤性脑损伤（TBI）后脑水肿和血脑屏障（BBB）功能障碍的程度影响创伤性脑损伤（TBI）后的神经功能结局。先前的研究已经证明，施用载脂蛋白E模拟肽COG 1410降低了蛛网膜下腔出血、脑内出血和局灶性脑缺血后的脑含水量。然而，COG 1410对TBI后血管源性水肿的作用尚不清楚。本研究评价了在小鼠中，在急性阶段，在受控皮质撞击（CCI）损伤后静脉内给予每日lmg/kg的COG 1410与生理盐水相比对BBB功能障碍和血管源性水肿的影响。结果表明，在CCI后的急性阶段，与用载体处理的小鼠相比，用COG 1410处理抑制了基质金属蛋白酶-9的活性，减少了BBB的破坏和伊文思蓝染料外渗，减少了TBI损伤体积和血管源性水肿，并减少了功能缺陷。这些发现表明，COG 1410是一个有前途的临床前治疗剂，用于治疗创伤性脑损伤。
The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury.