Cortical spreading depression activates trophic factor expression, in neurons and astrocytes and protects against subsequent focal brain Ischemia
Cortical spreading depression activates trophic factor expression, in neurons and astrocytes and protects against subsequent focal brain Ischemia
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DOI：
10.1016/s0006-8993(98)00716-1
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发表时间：
1998-10-05
期刊：
影响因子：
2.9
通讯作者：
Hakim, AM
中科院分区：
文献类型：
--
作者：
Matsushima, K;Schmidt-Kastner, R;Hakim, AM
我们最近报道，皮质扩散性抑制（CSD），用于预处理大鼠脑，减少皮质梗死体积所造成的局灶性脑缺血大脑中动脉闭塞（MCAO）3天后。CSD这种保护作用的机制仍有待探讨。在这项研究中，我们证实，CSD是神经保护时，氯化钾是脑内，而不是皮质内应用。新皮质梗死体积在火腿组和CSD组分别为101.3 ± 48.5 mm（3）和45.3 ± 44.1 mm（3）（p < 0.05）。使用图像分析，我们确定了皮质区幸免于梗死的前CSD。然后，我们确定了脑源性神经营养因子（BDNF）和碱性成纤维细胞生长因子（bFGF）的mRNA的分布和表达的时间过程中的动物组与CSD及其控制。我们还研究了星形胶质细胞CSD使用胶质细胞酸性蛋白（GFAP）作为标记物的反应。原位杂交（在0，3，12，24，72或168小时后CSD）显示，脑源性神经营养因子mRNA的显着升高后，CSD立即在周围的分布备用皮质，而bFGF mRNA上升CSD后12小时，出现更多的缺血区域的核心。免疫组织化学（在CSD后1、3或7天进行）显示新皮质中的GFAP，在CSD后3天达到峰值。热休克蛋白72（HSP 72）的表达不受CSD的影响。我们的结论是，上调的营养因子和胶质细胞的激活可能有助于CSD诱导的神经保护作用。(C)1998 Elsevier Science B.V.保留所有权利。
We recently reported that cortical spreading depression (CSD), used to precondition rat brain, reduced cortical infarction volume resulting from focal cerebral ischemia by middle cerebral artery occlusion (MCAO) 3 days later. The mechanisms underlying this protective effect by CSD remains to be explored. In this study, we confirm that CSD is neuroprotective when KCl is applied epidurally rather than intracortically. Neocortical infarct volume was 101.3 +/- 48.5 mm(3) and 45.3 +/- 44.1 mm(3) in the ham and CSD group, respectively (p < 0.05). Using image analysis, we identified the cortical region spared from infarction by the prior CSD. We then determined the distribution of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) mRNA and the time course of their expression in groups of animals treated with CSD and their controls. We also examined the response of astrocytes to CSD using glial fibrillary acidic protein (GFAP) as a marker. In situ hybridization (done at 0, 3, 12, 24, 72 or 168 h after CSD) showed significant elevation of BDNF mRNA in the cortex immediately after CSD in a distribution surrounding the spared cortex, while bFGF mRNA rose 12 h after CSD and appeared more within the core of the ischemic region. Immunohistochemistry (done at 1, 3 or 7 days after CSD) demonstrated GFAP in the neocortex, with a peak at 3 days after CSD. Heat shock protein 72 (HSP72) expression was not affected by CSD. We concluded that upregulation of trophic factors and activation of glial cells may contribute to the neuroprotection induced by CSD. (C) 1998 Elsevier Science B.V. All rights reserved.