Usefulness of plasma oxidative biomarker in patients with acute cerebral infarction

血浆氧化生物标志物在急性脑梗死患者中的作用

• 批准号: 17591516
• 负责人: UNO Masaaki
• 金额: $ 2.18万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591516/
• 关键词: plasma biomarkers; oxidative stress; cerebral infarction; angiotensin II AT1 receptor blocker; free radical scavenger; Oxidized LDL; marker; cerebral infarction

1) We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups; GI (n=24) had cortical lesions, GII (n=27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n =13; GIIa, n =14) and its efficacy was studied by comparing their plasma OxLDL-, S-100B-, and MnSOD levels to those in patients without edaravone (GIb, n=11, GII, n=13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa-than GIb patients (0.177±0.024 ng/μg apoB vs. 0.219±0.026, p<0.05). In GII patients, pre-and post-treatment plasma OxLDL was not significantly different (0.156±0.013 vs. 0.152±0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (p<0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb pati … More ents. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.2) Candesartan, an angiotensin II (Ang II) AT1 receptor blocker (ARB), is protective against cerebral ischemia in hypertensive rats. To elucidate the blood pressure-independent mechanisms underlying this protection we used normotensive rats in our in vivo-and human umbilical endothelial cells (HUVEC) in our in vitro experiments. Wistar rats were subjected to 2-hr middle cerebral artery (MCA) occlusion-reperfusion after 2-week pretreatment with ARB (0.5 or 1 mg/kg/day). HUVEC were stimulated with an optimal concentration of candesartan with or without Ang II. In ARB-treated normotensive rats, the cortical infarct volume was decreased. This was associated with a decrease in oxidative damage and hypoxia, and an increase in the expression of eNOS protein in the cortical penumbra and of eNOS mRNA in the MCA. In HUVEC, both ARB and Ang II increased eNOS protein expression. Ang II increased intracellular ROS and NO production and led to eNOS "uncoupling" to form superoxide. While ARB inhibited these increases, it increased the extracellular NO release and the protein expression of heme oxygenase-1 in the absence and presence of Ang II, suggesting that ARB directly enhanced NO availability and anti-oxidative effects. Ours is the first documentation that ARB increases endothelial function and anti-oxidative defense system, thereby contributing to the protection of the cortical penumbra against cerebral ischemia. The improvement by ARB of post-ischemic endothelial dysfunction via blood pressure-and Ang II-independent mechanisms may represent a therapeutic means of protecting against the consequences of cerebral ischemia. Less

1) 我们评估了血浆生物标志物的可用性，以监测脑损伤和依达拉奉的治疗效果。该研究由 51 名患有缺血性脑梗塞的患者组成。他们被分为 2 组； GI（n = 24）有皮质病变，GII（n = 27）有基底节或脑干病变。 27 名随机选择的患者（GIa，n = 13；GIIa，n = 14）服用依达拉奉，通过比较他们的血浆 OxLDL-、S-100B- 和 MnSOD 水平与未服用依达拉奉的患者（GIb，n = 11，GII，n = 13）来研究其疗效。开始使用依达拉奉三天后，GIa 患者的血浆 OxLDL 显着低于 GIb 患者（0.177±0.024 ng/μg apoB vs. 0.219±0.026，p<0.05）。在 GII 患者中，治疗前和治疗后血浆 OxLDL 没有显着差异（0.156±0.013 与 0.152±0.020）。在GIa患者中，S-100B和MnSOD显着低于GIb患者（p<0.05）。 GIa 患者出院时的神经系统状况已恢复，但 GIb 患者并未恢复。我们的证据是通过血浆生物标志物证实依达拉奉功效的第一个证据。在皮质梗塞患者中，依达拉奉可减少氧化损伤，从而限制脑损伤程度。2) 坎地沙坦是一种血管紧张素 II (Ang II) AT1 受体阻滞剂 (ARB)，可预防高血压大鼠的脑缺血。为了阐明这种保护作用背后的与血压无关的机制，我们在体内实验中使用了血压正常的大鼠，在体外实验中使用了人脐带内皮细胞（HUVEC）。 Wistar 大鼠在用 ARB（0.5 或 1 mg/kg/天）预处理 2 周后进行 2 小时大脑中动脉（MCA）闭塞再灌注。用最佳浓度的坎地沙坦（含或不含 Ang II）刺激 HUVEC。在接受 ARB 治疗的正常血压大鼠中，皮质梗塞体积减少。这与氧化损伤和缺氧的减少以及皮质半影中 eNOS 蛋白和 MCA 中 eNOS mRNA 表达的增加有关。在 HUVEC 中，ARB 和 Ang II 均增加 eNOS 蛋白表达。 Ang II 增加细胞内 ROS 和 NO 的产生，并导致 eNOS“解偶联”形成超氧化物。虽然 ARB 抑制了这些增加，但在 Ang II 不存在和存在的情况下，它增加了细胞外 NO 的释放和血红素加氧酶-1 的蛋白表达，表明 ARB 直接增强了 NO 的可用性和抗氧化作用。我们的研究首次证明 ARB 可以增强内皮功能和抗氧化防御系统，从而有助于保护皮质半暗带免受脑缺血的影响。 ARB 通过血压和 Ang II 独立机制改善缺血后内皮功能障碍，这可能是一种预防脑缺血后果的治疗方法。较少的

项目成果

Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and postoperative diffusion-weighted imaging.

通过术中监测和术后弥散加权成像评估颈动脉内膜切除术期间的血流动力学脑缺血。

• 发表时间: 2007
• 期刊: Neurol Res 29
• 作者: Hashiba Tetsuo;Hashiba Tetsuo;Hashiba Tetsuo;Oshino Satoru;Kagawa Naoki;Hashiba Tetsuo;Morita Satoshi;Oshino Satoru;Hashiba Tetsuo;Morita Satoshi;Hashiba Tetsuo;Suzuki Tsuyoshi;Fujimoto Yasunori;Izumoto Shuichi;Kinoshita Manabu;Moriuchi Shusuke;Suzuki Tsuyoshi;Wada Kouichi;Suzuki Tsuyoshi;Kinoshita Manabu;Moriuchi Syusuke;Suzuki Tsuyoshi;Kinoshita Manabu;Wada Kouichi;Masaaki Uno;宇野昌明;Masaaki Uno
• 通讯作者: Masaaki Uno

Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis. Two cases reports

偏侧舞蹈症是由于与颅外颈动脉狭窄相关的血流动力学缺血所致。

• 发表时间: 2006
• 期刊: J Neurosurg 105
• 作者: Hashiba Tetsuo;Hashiba Tetsuo;Hashiba Tetsuo;Oshino Satoru;Kagawa Naoki;Hashiba Tetsuo;Morita Satoshi;Oshino Satoru;Hashiba Tetsuo;Morita Satoshi;Hashiba Tetsuo;Suzuki Tsuyoshi;Fujimoto Yasunori;Izumoto Shuichi;Kinoshita Manabu;Moriuchi Shusuke;Suzuki Tsuyoshi;Wada Kouichi;Suzuki Tsuyoshi;Kinoshita Manabu;Moriuchi Syusuke;Suzuki Tsuyoshi;Kinoshita Manabu;Wada Kouichi;Masaaki Uno;宇野昌明;Masaaki Uno;Masaaki Uno;宇野昌明;Ryoma Morigaki
• 通讯作者: Ryoma Morigaki

頚動脈内膜剥離術。VII 頚動脈狭窄 : インターベンション時代の脳卒中学(改訂第2版)下。-超急性期から再発予防まで-

颈动脉内膜切除术。

• 发表时间: 2006
• 作者: Hashiba Tetsuo;Hashiba Tetsuo;Hashiba Tetsuo;Oshino Satoru;Kagawa Naoki;Hashiba Tetsuo;Morita Satoshi;Oshino Satoru;Hashiba Tetsuo;Morita Satoshi;Hashiba Tetsuo;Suzuki Tsuyoshi;Fujimoto Yasunori;Izumoto Shuichi;Kinoshita Manabu;Moriuchi Shusuke;Suzuki Tsuyoshi;Wada Kouichi;Suzuki Tsuyoshi;Kinoshita Manabu;Moriuchi Syusuke;Suzuki Tsuyoshi;Kinoshita Manabu;Wada Kouichi;Masaaki Uno;宇野昌明;Masaaki Uno;Masaaki Uno;宇野昌明;Ryoma Morigaki;Naomi Morita;Naomi Morita;Masaaki Uno;Masaaki Uno;Masaaki Uno;Kazuhito Matsuzaki;Masaaki Uno;Masaaki Uno;Masaaki Uno;Kazuhito Matsuzaki;宇野昌明
• 通讯作者: 宇野昌明

Anaplastic ganglioglioma of the cerebellopontine angle - Case report

• DOI: 10.2176/nmc.45.591
• 发表时间: 2005-11-01
• 期刊: NEUROLOGIA MEDICO-CHIRURGICA
• 影响因子: 1.9
• 作者: Matsuzaki, K;Uno, M;Nagahiro, S
• 通讯作者: Nagahiro, S

Change of diffusion anisotropy in patients with acute cerebral infarction using statistical parametric analysis.

• DOI: 10.1007/s11604-005-1535-z
• 发表时间: 2006-05-01
• 期刊: Radiation medicine
• 作者: Morita, Naomi;Harada, Masafumi;Nishitani, Hiromu
• 通讯作者: Nishitani, Hiromu