Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats.
Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats.
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DOI：
10.1002/cne.22039
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Airavaara M;Shen H;Kuo CC;Peränen J;Saarma M;Hoffer B;Wang Y
中脑星形胶质细胞源性神经营养因子（MANF），也称为富含精氨酸的肿瘤早期突变（ARMET），是一种分泌性蛋白，可减少内质网（ER）应激。先前的研究表明，MANF mRNA表达和蛋白水平在脑缺血后的大脑皮层中增加，这是一种诱导ER应激的条件。MANF在脑缺血中的作用尚不清楚。本研究旨在探讨MANF对缺血性脑损伤的保护作用。在成年大鼠大脑中动脉闭塞（MCAo）60分钟之前，将重组人MANF局部施用到大脑皮层。氯化三苯基四氮唑（TTC）染色表明，MANF预处理后两天的梗死体积显着减少MCAo。MANF还减弱了缺血皮质中细胞坏死/凋亡的标记物TUNEL标记。接受MANF预处理的动物表现出身体不对称性和神经评分的降低以及MCAo后运动活性的增加。总之，这些数据表明，MANF对脑缺血具有神经保护作用，可能是通过抑制大脑皮层细胞坏死/凋亡。
Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as Arginine-rich, Mutated in Early Stage of Tumors (ARMET), is a secreted protein which reduces endoplasmic reticulum (ER) stress. Previous studies have shown that MANF mRNA expression and protein levels are increased in the cerebral cortex after brain ischemia, a condition which induces ER stress. The function of MANF during brain ischemia is still not known. The purpose of this study was to examine the protective effect of MANF after ischemic brain injury. Recombinant human MANF was administrated locally to the cerebral cortex before a 60-min middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium chloride (TTC) staining indicated that pretreatment with MANF significantly reduced the volume of infarction at two days after MCAo. MANF also attenuated TUNEL labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex.
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