Time-dependent and lesion-dependent HMGB1-selective localization in brains of patients with cerebrovascular diseases
Time-dependent and lesion-dependent HMGB1-selective localization in brains of patients with cerebrovascular diseases
复制标题
DOI：
10.14670/hh-11-914
复制
发表时间：
2018-02-01
影响因子：
2
通讯作者：
Hanyu, Haruo
中科院分区：
文献类型：
--
作者：
Umahara, Takahiko;Uchihara, Toshiki;Hanyu, Haruo
高迁移率族蛋白1（HMGB1）具有维持核小体和调控基因转录等多种功能。HMGB1从活化的巨噬细胞释放，导致诱导炎性细胞因子。近年来，关于HMGB1在脑血管病（CVD）中的作用的研究报道较多。在动物模型中，HMGB1中和可改善脑梗死，HMGB1从神经元中早期释放，HMGB1抗体可减轻实验性蛛网膜下腔出血中的迟发性脑血管痉挛。也有研究表明，血清HMGB1水平升高与急性脑出血的严重程度相关，但HMGB1在脑血管病患者脑内的定位证据非常有限。因此，我们在尸检时研究了CVD（急性和慢性脑梗死、急性脑出血、蛛网膜下腔出血）患者脑中HMGB1的免疫定位。在10例急性脑梗死病例中的3例中，神经元的细胞质位于缺血核心周围（即，半暗带）为HMGB1阳性。脑梗死慢性期部分缺血区巨噬细胞呈HMGB1阳性。在基底节血肿周围，巨噬细胞中HMGB1样免疫反应性（IR）强。然而，在蛛网膜下腔血肿周围，在皮质中未观察到HMGB1样IR。在蛛网膜下腔血肿周围的动脉中，HMGB1样IR位于血管平滑肌细胞的胞浆中。这些发现与动物模型结果部分不同，可能为理解HMGB1在CVD患者大脑中的作用提供转化研究和基础。
High mobility group box 1 protein (HMGB1) has multiple functions, including the maintenance of nucleosomes and the regulation of gene transcription. HMGB1 is released from activated macrophages, resulting in the induction of inflammatory cytokines. Recently, much research about the role of HMGB1 in cerebrovascular disease (CVD) has been reported. In an animal model, HMGB1 neutralization ameliorates brain infarction, there is an early release of HMGB1 from neurons, and HMGB1 antibody attenuates delayed cerebral vasospasm in experimental subarachnoid hemorrhage. It was also reported that elevation of HMGB1 in serum correlates with severity of acute intracerebral hemorrhage.However, the evidence of HMGB1 localization in brains of patients with CVD is very limited. Therefore, we investigated at autopsy the immunolocalization of HMGB1 in brains of patients with CVD (acute and chronic cerebral infarction, acute cerebral hemorrhage, subarachnoid hemorrhage).In 3 out of 10 acute cerebral infarction cases, the cytoplasm of neurons located around the ischemic core (i.e., penumbra) was positive for HMGB1. In the chronic stage of cerebral infarction, macrophages located in some ischemic regions were positive for HMGB1. Around the hematoma in the basal ganglia, HMGB1-like immunoreactivity (IR) was intense in macrophages. However, around the subarachnoid hematoma, HMGB1-like IR was not seen in the cortex. In arteries surrounded by subarachnoid hematoma, HMGB1-like IR was located in the cytoplasm of vascular smooth muscle cells. These findings, which partially differ from animal model results, may provide translational research and a basis for understanding the role of HMGB1 in brains of patients with CVD.