Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain
Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain
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DOI：
10.1007/s002210100715
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发表时间：
2001-06-01
影响因子：
2
通讯作者：
Finsen, B
中科院分区：
文献类型：
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作者：
Gregersen, R;Christensen, T;Finsen, B
虽然少突胶质细胞易受局灶性脑缺血的影响，但在中枢神经系统中已观察到梗死周围区域中裸露或再生轴突的髓鞘再生。我们研究了髓鞘碱性蛋白（MBP）的表达，中枢神经系统髓鞘的主要成分，在梗死周围地区的成年大鼠大脑短暂大脑中动脉闭塞（MCAO）后，并将其与生长相关蛋白-43（GAP-43）的表达，轴突再生和发芽的标志物，使用非放射性原位杂交技术。在梗死，MBP信使RNA（mRNA）已消失24小时，而髓鞘蛋白，MBP和髓鞘少突胶质细胞糖蛋白（MOG）免疫组化鉴定，出现结构完整，直到第3天。梗死周围的少突胶质细胞的MBP mRNA的表达从24小时增加到最高水平，在第7天，相应的过程轴承MBP和偶尔MOG免疫反应性少突胶质细胞的平行部分的外观。定量分析显示，少突胶质细胞的密度显着增加（高达7.6倍）和单个细胞表达的MBP mRNA的水平。平行切片显示，少突胶质细胞中MBP mRNA表达上调与神经元中GAP-43 mRNA表达上调同时发生。虽然调节少突胶质细胞存活和髓鞘形成信号的机制在这一点上还不清楚，轴突发芽可以作为一个刺激的少突胶质细胞数量，分化状态，和/或活跃的髓鞘形成在梗死周围地区的上调。
Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin, in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using nonradioactive in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cells. Parallel sections showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation of oligodendrocyte cell numbers, differentiation state, and/or active myelination in the peri-infarct areas.