Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Tanta University, El-Geish Street, Tanta, El-Gharbia, Egypt.
Department of Neuropsychiatry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Neurol Sci. 2018 Jun;39(6):1093-1104. doi: 10.1007/s10072-018-3396-0. Epub 2018 Apr 10.
Acute ischemic stroke (AIS) is followed by a strong inflammatory response contributing to brain damage and making early diagnosis and treatment inevitable. Hence, obesity is a state of chronic inflammation with amplified oxidative stress; this study aimed to assess the role played by thrombomodulin (TM)/alarmin signaling pathway and copeptin in AIS initiation and severity in addition to the implication of abnormal body weight. The study was conducted on 50 participants; 30 were patients with AIS (15 overweight/obese and 15 normal weight), 10 were overweight/obese, and 10 were normal weight. Plasma TM, copeptin, high mobility group box1 (HMGB1), and lipocalin 2 (LCN2) levels were immunoassayed. Toll-like receptor 4 (TLR4) mRNA expression was evaluated by real-time PCR, National Institutes of Health Stroke Scale (NIHSS), carotid intima media thickness; atherogenic index and glycemic status were also assessed. TM, copeptin, HMGB1, and LCN2 levels were significantly increased in overweight/obese AIS patients and in AIS patients with NIHSS score ≥ 7 when compared to other groups (p value=, ˂ 0.001*). Receiver operating characteristic (ROC) curve elaborated HMGB-1 and LCN2 as the best biomarker for diagnosis and prediction of AIS severity, respectively. Regression analysis avails LCN2 and TM as best biomarker for AIS severity predication. In conclusion, these results highlighted detrimental role of alarmin signaling with increased adaptive response to block this pathway through TM in addition to increased copeptin level as an acute damage marker and their tight relation to WC not to BMI in AIS which clarify the implication of central adiposity.
急性缺血性脑卒中（AIS）后会引发强烈的炎症反应，导致脑损伤，因此早期诊断和治疗是必不可少的。肥胖是一种慢性炎症状态，伴有放大的氧化应激；本研究旨在评估血栓调节蛋白（TM）/警报素信号通路和copeptin 在 AIS 发病和严重程度中的作用，以及异常体重的影响。该研究共纳入 50 名参与者；30 名是 AIS 患者（15 名超重/肥胖，15 名体重正常），10 名超重/肥胖，10 名体重正常。通过免疫测定法检测血浆 TM、copeptin、高迁移率族蛋白 B1（HMGB1）和脂联素 2（LCN2）水平。通过实时 PCR 评估 Toll 样受体 4（TLR4）mRNA 表达，采用美国国立卫生研究院卒中量表（NIHSS）、颈动脉内膜中层厚度；还评估了动脉粥样硬化指数和血糖状态。与其他组相比，超重/肥胖 AIS 患者和 NIHSS 评分≥7 的 AIS 患者的 TM、copeptin、HMGB1 和 LCN2 水平显著升高（p 值<0.001*）。受试者工作特征（ROC）曲线表明 HMGB-1 和 LCN2 分别是诊断和预测 AIS 严重程度的最佳生物标志物。回归分析表明 LCN2 和 TM 是预测 AIS 严重程度的最佳生物标志物。综上所述，这些结果强调了警报素信号通路的有害作用，并通过 TM 增加适应性反应来阻断该通路，此外，copeptin 水平升高作为急性损伤标志物及其与 WC 的紧密关系（而不是 BMI）在 AIS 中得到证实，这阐明了中心性肥胖的影响。
