Matsumoto Atsushi, Nakamura Takehiro, Shinomiya Aya, Kawakita Kenya, Kawanishi Masahiko, Miyake Keisuke, Kuroda Yasuhiro, Keep Richard F, Tamiya Takashi
Department of Neurological Surgery, Kagawa University Faculty of Medicine, Miki, Kagawa 761-0793, Japan.
Acta Med Okayama. 2019 Feb;73(1):29-39. doi: 10.18926/AMO/56456.
Cerebral vasospasm (CVS) is a major contributor to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. We measured histidine-rich glycoprotein (HRG), a new biomarker of aSAH, in cerebrospinal fluid (CSF) to investigate whether HRG might be an early predictor of CVS. A total of seven controls and 14 aSAH patients (8 males, 6 females aged 53.4±15.4 years) were enrolled, and serial CSF and serum samples were taken. We allocated these samples to three phases (T1-T3) and measured HRG, interleukin (IL)-6, fibrinopeptide A (FpA), and 8-hydroxy-2'-deoxyguanosine (8OHdG) in the CSF, and the HRG in serum. We also examined the release of HRG in rat blood incubated in artificial CSF. In contrast to the other biomarkers examined, the change in the CSF HRG concentration was significantly different between the nonspasm and spasm groups (p<0.01). The rat blood/CSF model revealed a time course similar to that of the human CSF samples in the non-spasm group. HRG thus appears to have the potential to become an early predictor of CVS. In addition, the interaction of HRG with IL-6, FpA, and 8OHdG may form the pathology of CVS.
脑血管痉挛(CVS)是导致动脉瘤性蛛网膜下腔出血(aSAH)患者高发病率和高死亡率的主要因素。我们检测了脑脊液(CSF)中富含组氨酸的糖蛋白(HRG),这是一种aSAH的新生物标志物,以研究HRG是否可能是CVS的早期预测指标。共纳入7名对照者和14例aSAH患者(8例男性,6例女性,年龄53.4±15.4岁),并采集了系列脑脊液和血清样本。我们将这些样本分为三个阶段(T1-T3),检测脑脊液中的HRG、白细胞介素(IL)-6、纤维蛋白肽A(FpA)和8-羟基-2'-脱氧鸟苷(8OHdG),以及血清中的HRG。我们还检测了在人工脑脊液中孵育的大鼠血液中HRG的释放情况。与其他检测的生物标志物不同,非痉挛组和痉挛组脑脊液中HRG浓度的变化有显著差异(p<0.01)。大鼠血液/脑脊液模型显示出与非痉挛组人类脑脊液样本相似的时间进程。因此,HRG似乎有可能成为CVS的早期预测指标。此外,HRG与IL-6、FpA和8OHdG的相互作用可能形成CVS的病理过程。