Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system.
Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system.
复制标题
中枢神经系统中促红细胞生成素受体无效的小鼠创伤性脑损伤后的组织学和功能结果。
DOI：
10.1016/j.brainres.2008.06.127
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发表时间：
2008-09-16
期刊：
影响因子：
2.9
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Xiong, Ye;Mahmood, Asim;Lu, Dunyue;Qu, Changsheng;Kazmi, Humaira;Goussev, Anton;Zhang, Zheng Gang;Noguchi, Constance T.;Schallerte, Timothy;Chopp, Michael
关键词：
促红细胞生成素 (EPO) 及其受体 (EPOR) 对红细胞生成至关重要，在神经系统中表达。重组人 EPO 治疗可促进创伤性脑损伤 (TBI) 和中风后的功能恢复，表明内源性 EPO/EPOR 系统在神经保护和神经恢复中发挥重要作用。本研究旨在调查 EPOR 对 TBI 后组织学和功能结果的影响。通过控制皮质冲击，在成年 EPOR 无效小鼠和野生型小鼠中诱导实验性 TBI。使用改良的莫里斯水迷宫和足误测试来评估神经功能。受伤后 35 天处死动物，并对脑切片进行免疫组织化学染色。与野生型受伤小鼠相比，EPOR 缺失小鼠并未表现出对 TBI 更高的易感性，例如皮质组织损失、齿状回细胞损失、空间学习受损、血管生成和细胞增殖。我们观察到，TBI 后 EPOR 缺失小鼠的皮质神经发生较少，感觉运动功能（即足错）受损更严重。 TBI 后，EPOR 缺失小鼠和野生型小鼠的同侧丘脑中观察到淀粉样前体蛋白（轴突损伤标志物）和钙的共同积累，而野生型小鼠中存在更多的钙沉积。这项研究首次证明，神经系统中的 EPOR 缺失会加剧 TBI 后感觉运动缺陷、损害皮质神经发生并减少丘脑钙沉淀。
Erythropoietin (EPO) and its receptor (EPOR), essential for erythropoiesis, are expressed in the nervous system. Recombinant human EPO treatment promotes functional outcome after traumatic brain injury (TBI) and stroke, suggesting that the endogenous EPO/EPOR system plays an important role in neuroprotection and neurorestoration. This study was designed to investigate effects of the EPOR on histological and functional outcomes after TBI. Experimental TBI was induced in adult EPOR-null and wild-type mice by controlled cortical impact. Neurological function was assessed using the modified Morris Water Maze and footfault tests. Animals were sacrificed 35 days after injury and brain sections stained for immunohistochemistry. As compared to the wild-type injured mice, EPOR-null mice did not exhibit higher susceptibility to TBI as exemplified by tissue loss in the cortex, cell loss in the dentate gyrus, impaired spatial learning, angiogenesis and cell proliferation. We observed that less cortical neurogenesis occurred and that sensorimotor function (i.e., footfault) was more impaired in the EPOR-null mice after TBI. Co-accumulation of amyloid precursor protein (axonal injury marker) and calcium was observed in the ipsilateral thalamus in both EPOR-null and wild-type mice after TBI with more calcium deposits present in the wild-type mice. This study demonstrates for the first time that EPOR null in the nervous system aggravates sensorimotor deficits, impairs cortical neurogenesis and reduces thalamic calcium precipitation after TBI.
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