Cell death and proliferation in NF-κB p50 knockout mouse after cerebral ischemia
Cell death and proliferation in NF-κB p50 knockout mouse after cerebral ischemia
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DOI：
10.1016/j.brainres.2008.06.130
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发表时间：
2008-09-16
期刊：
影响因子：
2.9
通讯作者：
Wei, Ling
中科院分区：
文献类型：
--
作者：
Li, Jimei;Lu, Zhongyang;Wei, Ling
转录因子NF-κ B是炎症和细胞存活的关键调节因子。脑缺血后NF-κ B B活化增加。我们先前在生理条件下显示了NF-κ B B p50亚基敲除（p50（-/-））小鼠的加速老化过程。本研究探讨NF-κ B B p50基因在缺血诱导的神经细胞死亡中的作用。在永久性大脑中动脉闭塞（MCAO）的动物模型中，在成年野生型（WT）和p50（-/-）小鼠中检查梗塞形成、凋亡性细胞死亡和细胞增殖。p50（-/-）小鼠脑梗死体积明显大于WT小鼠。p50（-/-）小鼠海马半暗带区末端脱氧核苷酸转移酶（TdT）介导的dUTP-生物素缺口末端标记（TUNEL）和caspase-3染色阳性细胞数明显多于WT小鼠。为了鉴定脑缺血后的增殖，MCAO后每天腹腔注射溴脱氧尿苷（BrdU）。缺血增加BrdU阳性细胞在半影区，脑室下区，胼胝体，大脑皮层，而细胞增殖在p50（-/-）小鼠受到阻碍。这些结果表明，NF-κ B B信号是一种神经保护机制，可能在永久性MCAO中风模型的细胞增殖中发挥作用。(C)2008 Elsevier B. V.保留所有权利。
The transcription factor NF-kappa B is a key regulator of inflammation and cell survival. NF-kappa B activation increases following cerebral ischemia. We previously showed accelerated aging process in NF-kappa B p50 subunit knockout (p50(-/-)) mice under physiological condition. The present investigation concerned the role of NF-kappa B p50 gene in ischemia-induced neuronal cell death. In an animal model of permanent middle cerebral artery occlusion (MCAO), infarct formation, apoptotic cell death and cell proliferation were examined in adult wild type (WT) and p50(-/-) mice. The ischemic infarct volume was significantly larger in p50(-/-) mice than that in WT mice. Consistently, the numbers of cells in the penumbra region positive to terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) and caspase-3 staining were significantly more in p50(-/-) mice than that in WT mice. To identify proliferation after cerebral ischemia, bromodeoxyurindine (BrdU) was intraperitoneal injected daily after MCAO. Ischemia increased BrdU positive cells in the penumbra, subventricular zone, corpus callosum, and cerebral cortex, while cell proliferation was hampered in p50(-/-) mice. These results suggest that NF-kappa B signaling is a neuroprotective mechanism and may play a role in cell proliferation in the stroke model of permanent MCAO. (C) 2008 Elsevier B.V. All rights reserved.