Slevin M, Krupinski J, Slowik A, Rubio F, Szczudlik A, Gaffney J
Department of Biological Sciences, Manchester Metropolitan University, UK.
Neuroreport. 2000 Aug 21;11(12):2759-64. doi: 10.1097/00001756-200008210-00030.
We examined expression of vascular endothelial growth factor (VEGF), phosphorylation of mitogen activated protein kinase (MAP) kinase (ERK1 and ERK2) and tyrosine phosphorylation in 19 patients (aged 58-90 years; mean 75) who died 1-44 days after acute ischaemic stroke. In the grey matter penumbra, 13 of 19 patients showed an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 8-fold, ERK2; 2.2- to 11-fold) compared with normal contralateral tissue. In almost all cases, ERK-2 phosphorylation was higher than ERK1. Of these 13 patients, 11 also showed a general increase in tyrosine kinase phosphorylation, and eight expressed increased levels of VEGF protein (2.5- to 5-fold). In tissue examined directly from the infarct core, activation of the above proteins was not observed in the, majority of patients. In the white matter, seven of 19 patients (penumbra), and nine of 19 patients (stroke) had an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 4.6-fold and ERK-2; 2.3- to 5.4-fold respectively) compared with normal contralateral tissue. There was no relationship between activation of MAP kinase and expression of VEGF. Examination of phosphorylated MAP kinase by immunohistochemistry revealed an increase in immunoreactivity in neurones, astroglial cells, reactive microglia and endothelial cells in areas surrounding infarcts, especially in areas with the highest density of microvessels. In conclusion, chronic activation of tyrosine phosphorylated events, in particular redistribution and phosphorylation of MAP kinase (ERK1/ERK2) occurs consistently in the grey matter penumbra of brain tissue following ischaemic stroke, and may be associated with increase in expression of VEGF. These signal transduction events could be important determinants of the extent of neuronal survival and/or angiogenic activity in the recovering brain tissue.
我们检测了19例急性缺血性卒中后1 - 44天死亡患者（年龄58 - 90岁，平均75岁）血管内皮生长因子（VEGF）的表达、丝裂原活化蛋白激酶（MAP激酶，即ERK1和ERK2）的磷酸化以及酪氨酸磷酸化情况。在灰质半暗带，19例患者中有13例与对侧正常组织相比，MAP激酶酪氨酸磷酸化增加（ERK1增加2.0至8倍，ERK2增加2.2至11倍）。几乎在所有病例中，ERK - 2的磷酸化高于ERK1。在这13例患者中，11例还表现出酪氨酸激酶磷酸化普遍增加，8例VEGF蛋白表达水平升高（2.5至5倍）。在直接取自梗死核心的组织中，大多数患者未观察到上述蛋白的激活。在白质中，19例患者中有7例（半暗带）和9例（卒中区域）与对侧正常组织相比，MAP激酶酪氨酸磷酸化增加（ERK1分别增加2.0至4.6倍，ERK - 2增加2.3至5.4倍）。MAP激酶的激活与VEGF的表达之间没有关系。通过免疫组织化学检测磷酸化MAP激酶发现，梗死周围区域的神经元、星形胶质细胞、反应性小胶质细胞和内皮细胞中的免疫反应性增加，尤其是在微血管密度最高的区域。总之，酪氨酸磷酸化事件的慢性激活，特别是MAP激酶（ERK1 / ERK2）的重新分布和磷酸化，在缺血性卒中后脑组织的灰质半暗带中持续发生，并且可能与VEGF表达增加有关。这些信号转导事件可能是恢复中的脑组织中神经元存活范围和/或血管生成活性的重要决定因素。
