Activation of vascular endothelial cells and perivascular cells by systemic inflammation-an immunohistochemical study of postmortem human brain tissues
Activation of vascular endothelial cells and perivascular cells by systemic inflammation-an immunohistochemical study of postmortem human brain tissues
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DOI：
10.1007/s00401-003-0815-x
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发表时间：
2004-04-01
影响因子：
12.7
通讯作者：
Kosaka, K
中科院分区：
文献类型：
--
作者：
Uchikado, H;Akiyama, H;Kosaka, K
我们研究了死后的人脑组织，以确定全身炎症是否会导致血管内皮细胞和血管周围细胞的激活。在某些情况下，我们使用急性期反应物C反应蛋白(CRP)的血清浓度作为全身炎症的指标。由于急性期的血清CRP浓度仅在有限数量的患者中可用，我们通过脑组织残留血液中CRP的免疫组织化学染色强度来估计全身炎症的程度。以细胞间黏附分子(ICAM)-1、CD40和环氧合酶(COX)-2的表达作为血管内皮细胞活化的标志。血管周围细胞的活化程度由人类白细胞抗原DR和CD68阳性的血管周围细胞的出现来评估。在无脑损害的病例中，血管内皮细胞和血管周围细胞的激活与全身炎症程度有关。在有脑损伤的病例中，即使在没有全身炎症的情况下，这些细胞也经常被激活。我们认为，来自外周血和脑实质的炎性刺激辅助激活血管细胞。在这种情况下，先前存在的脑损伤中的低级别炎症可能会增强从外围到脑实质的炎症信号。这项研究的结果可以解释神经科患者易受全身炎症条件引起的精神错乱的影响。
We investigated postmortem human brain tissues to determine whether systemic inflammation causes activation of vascular endothelial cells and perivascular cells. In some cases, we used serum concentrations of an acute-phase reactant, C-reactive protein (CRP), as an index of systemic inflammation. Since the serum concentration of CRP at the agonal stage was available only in a limited number of patients, we estimated the degree of systemic inflammation by the intensity of immunohistochemical staining of the residual blood in brain tissue for CRP. Expressions of intercellular adhesion molecule (ICAM)-1, CD40 and cyclooxygenase (COX)-2 were used as markers for activation of vascular endothelial cells. Activation of perivascular cells was estimated by the occurrence of HLA-DR- and CD68-positive perivascular cells. In cases without brain lesions, activation of vascular endothelial cells and perivascular cells was related to the degree of systemic inflammation. In cases with brain lesions, these cells are often activated even in the absence of systemic inflammation. We suggest that inflammatory stimuli derived from the peripheral blood and the brain parenchyma adjunctly activate vascular cells. Under such circumstances, low-grade inflammation in the pre-existing brain lesions might enhance inflammatory signaling to the brain parenchyma from the periphery. The results of this study could explain the vulnerability of neurological patients to delirium caused by systemic inflammatory conditions.