Mindin is a critical mediator of ischemic brain injury in an experimental stroke model
Mindin is a critical mediator of ischemic brain injury in an experimental stroke model
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Mindin 是实验性中风模型中缺血性脑损伤的关键介质
DOI：
10.1016/j.expneurol.2013.01.022
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Li, Hongliang
中科院分区：
文献类型：
--
作者：
Jiang, Dingsheng;Dong, Xiaomin;Deng, Shan;Yang, Li;Guan, Yu;Zhu, Lihua;Zhou, Yan;Zhang, Xiaodong;Li, Hongliang
背景中风是全球成年人死亡的第二大原因。 Mindin 是一种 ECM 蛋白，在调节炎症、血管生成和神经元生长中发挥重要作用。 Mindin 在脑缺血中的作用尚未得到研究。方法和结果对 Mindin 敲除 (KO) 小鼠、携带神经元特异性组成型活跃 Mindin 转基因 (TG) 的小鼠和适当的对照小鼠进行大脑中动脉短暂闭塞。通过检查梗塞和水肿体积以及通过神经学评分评估来评估缺血的结果。诱发中风后 24 小时或 3 天收集大脑。与对照小鼠相比，mindin KO 小鼠在神经学测试中表现出更小的梗塞体积和更好的结果。 Mindin 缺陷小鼠表现出中风诱导的炎症介质的低表达水平、炎症细胞的募集减弱以及 NF-κB 的激活受到抑制。 Mindin KO 小鼠大脑中的神经元凋亡水平也低于对照小鼠。表达神经元特异性、组成性活跃的 Mindin 转基因的小鼠在脑缺血损伤后表现出与 Mindin KO 小鼠中观察到的相反的效果。此外，Mindin KO 小鼠缺血性大脑中的 Akt 信号激活升高。结论 Mindin KO 小鼠在缺血性损伤后表现出轻微的梗塞、炎症反应减弱和低水平的神经元凋亡。这些数据表明，mindin 是实验性中风模型中缺血性脑损伤的关键介质。在这种脑缺血模型中，Akt 信号传导很可能介导 Mindin 的生物学功能。
BackgroundStroke is the second leading cause of death among adults worldwide. Mindin is an ECM protein that plays important roles in regulating inflammation, angiogenesis and neuronal outgrowth. The role of mindin in the context of brain ischemia has not been examined.Methods and resultsTransient occlusion of the middle cerebral artery was performed on mindin knockout (KO) mice, mice that carried a neuron-specific constitutively active mindin transgene (TG) and the appropriate controls. The outcome of the ischemia was evaluated by examination of the infarct and edema volumes and by neurological score assessments. The brains were collected 24 h or 3 days following the induced stroke. Compared with the control mice, the mindin KO mice exhibited lower infarct volumes and better outcomes in the neurological tests. Mindin-deficient mice exhibited low expression levels of stroke-induced inflammatory mediators, an attenuated recruitment of inflammatory cells, and inhibited activation of NF-κB. The neuronal apoptosis levels were also lower in the brains of the mindin KO mice than in those of the control mice. The mice that expressed a neuron-specific, constitutively active mindin transgene exhibited effects following the cerebral ischemic injury that were the opposite of those that were observed in the mindin KO mice. Moreover, Akt signaling activation was elevated in the ischemic brains of mindin KO mice.ConclusionsMindin KO mice exhibited minor infarctions, an attenuated inflammatory response and low levels of neuronal apoptosis following an ischemic insult. These data demonstrate that mindin is a critical mediator of ischemic brain injury in an experimental stroke model. Akt signaling most likely mediates the biological function of mindin in this model of cerebral ischemia.
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影响因子：
4.6
作者：
Y. Feinstein;V. Borrell;C. García;T. Burstyn-Cohen;V. Tzarfaty;A. Frumkin;A. Nose;H. Okamoto;S. Higashijima;E. Soriano;A. Klar
通讯作者：
Y. Feinstein;V. Borrell;C. García;T. Burstyn-Cohen;V. Tzarfaty;A. Frumkin;A. Nose;H. Okamoto;S. Higashijima;E. Soriano;A. Klar
影响因子：
6
作者：
通讯作者：
--
影响因子：
4.4
作者：
Manda，R;Kohno，T;Yokota，J
通讯作者：
Yokota，J
影响因子：
37.8
作者：
Caso, Javier R.;Pradillo, Jesus M.;Lizasoain, Ignacio
通讯作者：
Lizasoain, Ignacio
DOI：
10.17816/rfd201244-12
发表时间：
2012-12
期刊：
Rossiĭskiĭ semeĭnyĭ vrach
影响因子：
--
作者：
D. Kandyba;В КандыбаД
通讯作者：
D. Kandyba;В КандыбаД