Gubits R M, Burke R E, Casey-McIntosh G, Bandele A, Munell F
Department of Neurology, University College of Physicians and Surgeons, New York, NY 10032.
Brain Res Mol Brain Res. 1993 May;18(3):228-38. doi: 10.1016/0169-328x(93)90194-t.
Immediate early gene (IEG) products, such as FOS and JUN, may partially mediate the long-term transcriptional response of CNS cells to specific changes in their environment. To determine whether IEG products might be involved in the immature brain's response to hypoxia-ischemia (H-I), 7-day-old rat pups were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia (8% O2/92% N2) at 37 degrees C, which results in pathological changes only in specific regions of the hemisphere ipsilateral to ligation. Time course experiments were performed, in which animals were sacrificed between 1 and 24 h after H-I. RNAs from several brain regions were analyzed by Northern blot hybridization for their relative concentrations of nine IEG mRNAs (c-fos, c-jun, junB, TIS 1 (nur77), TIS7, TIS8 (zif268), TIS10, TIS11, and TIS21). Induction of all IEGs, except TIS7 and TIS10, was observed in ipsilateral forebrain, and, less frequently, in contralateral forebrain, at 1, 2, and 3 h post-hypoxia. In some animals, lower levels of expression were also detected at 4, 18 and 24 h. With minor exceptions, co-induction of all seven IEGs was observed in a given RNA sample. Induction of two other mRNAs, representing the heat shock and astrocytic responses, were also observed. Hsp70 mRNA levels were increased only in the brains of animals exhibiting IEG induction. However, hsp70 induction was confined to the ipsilateral forebrain, implying a more direct relationship between its expression and permanent morphological damage. GFAP mRNA induction occurred predominantly in ipsilateral forebrain samples at 18 and 24 h post-hypoxia. Levels of B-actin and ubiquitin mRNAs were relatively constant in the same RNA samples. In control experiments c-fos mRNA induction was not detected after sham ligation with hypoxia, ligation with sham hypoxia, or hypoxia alone. These results suggest that the immature brain is highly responsive to H-I at the level of gene expression, involving at least three different rapid response systems.
即刻早期基因（IEG）产物，如FOS和JUN，可能部分介导中枢神经系统细胞对其环境中特定变化的长期转录反应。为了确定IEG产物是否可能参与未成熟脑对缺氧缺血（H-I）的反应，对7日龄大鼠幼崽进行单侧颈总动脉结扎，然后在37℃下进行3小时缺氧（8% O2/92% N2），这仅在结扎同侧半球的特定区域导致病理变化。进行了时间进程实验，在H-I后1至24小时处死动物。通过Northern印迹杂交分析来自几个脑区的RNA中九种IEG mRNA（c-fos、c-jun、junB、TIS 1（nur77）、TIS7、TIS8（zif268）、TIS10、TIS11和TIS21）的相对浓度。除TIS7和TIS10外，在缺氧后1、2和3小时，同侧前脑观察到所有IEG的诱导，对侧前脑较少见。在一些动物中，在4、18和24小时也检测到较低水平的表达。除少数例外，在给定的RNA样本中观察到所有七种IEG的共同诱导。还观察到另外两种代表热休克和星形细胞反应的mRNA的诱导。Hsp mRNA水平仅在表现出IEG诱导的动物脑中升高。然而，hsp70诱导仅限于同侧前脑，这意味着其表达与永久性形态损伤之间存在更直接的关系。GFAP mRNA诱导主要发生在缺氧后18和24小时的同侧前脑样本中。在相同的RNA样本中，β-肌动蛋白和泛素mRNA水平相对恒定。在对照实验中，假结扎加缺氧、假缺氧结扎或单独缺氧后未检测到c-fos mRNA诱导。这些结果表明，未成熟脑在基因表达水平上对H-I高度敏感，涉及至少三种不同的快速反应系统。
