Neuroglobin protects the brain from experimental stroke in vivo
Neuroglobin protects the brain from experimental stroke in vivo
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DOI：
10.1073/pnas.0637726100
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发表时间：
2003-03-18
影响因子：
11.1
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
--
作者：
Sun, YJ;Jin, KL;Greenberg, DA
脑红蛋白（Ngb）是一种O-2结合蛋白，定位于脊椎动物（包括人类）的大脑神经元。它的生理作用是未知的，但像血红蛋白，肌红蛋白和细胞珠蛋白/组织红蛋白，它可以运输O2，解毒活性氧，或作为缺氧传感器。我们最近报道，缺氧刺激Ngb在培养的皮层神经元的转录激活和Ngb表达的反义抑制增加缺氧神经元损伤，而Ngb的过度表达赋予耐缺氧。这些发现与Ngb在体外缺氧损伤后促进神经元存活的作用一致。在这里，我们报告说，在大鼠，脑室内管理的Ngb反义，而不是正义，寡脱氧核苷酸增加梗死体积和神经功能的结果，而脑内管理的Ngb表达腺相关病毒载体减少梗死面积和改善功能的结果，局灶性脑缺血后，大脑中动脉闭塞引起的。我们的结论是，Ngb作为一种内源性神经保护因子，在局灶性脑缺血，因此可能代表一个目标，为发展新的治疗中风。
Neuroglobin (Ngb) is an O-2-binding protein localized to cerebral neurons of vertebrates, including humans. Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport 02, detoxify reactive oxygen species, or serve as a hypoxia sensor. We reported recently that hypoxia stimulates transcriptional activation of Ngb in cultured cortical neurons and that antisense inhibition of Ngb expression increases hypoxic neuronal injury, whereas overexpression of Ngb confers resistance to hypoxia. These findings are consistent with a role for Ngb in promoting neuronal survival after hypoxic insults in vitro. Here we report that in rats, intracerebroventricular administration of an Ngb antisense, but not sense, oligodeoxynucleotide increases infarct volume and worsens functional neurological outcome, whereas intracerebral administration of a Ngb-expressing adeno-associated virus vector reduces infarct size and improves functional outcome, after focal cerebral ischemia induced by occlusion of the middle cerebral artery. We conclude that Ngb acts as an endogenous neuroprotective factor in focal cerebral ischemia and may therefore represent a target for the development of new treatments for stroke.