Current neurovascular research最新文献_第2页

Association between Peripheral Arterial Lactate Levels and Malignant Brain Edema Following Endovascular Treatment for Ischemic Stroke 缺血性脑卒中血管内治疗后外周动脉乳酸水平与恶性脑水肿之间的关系

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-12-15 DOI: 10.2174/0115672026283642231212061910

Huiyuan Wang, Ruozhen Yuan, Panpan Shen, Xinyue Yu, Xinyi Chen, Yafei Shang, Jie Xu, Mingming Tan, Sheng Zhang, Yu Geng

Aims: To investigate the factors of postoperative malignant brain edema (MBE) in patients with acute ischemic stroke (AIS) treated with endovascular treatment (EVT). Background: MBE is a severe complication following EVT for AIS, and it is essential to identify risk factors early. Peripheral arterial lactate (PAL) levels may serve as a potential predictive marker for MBE. Objective: To determine whether immediate postoperative PAL levels and the highest PAL level within 24 hours of EVT are independently associated with MBE development in AIS patients. Methods: We retrospectively analyzed patients with AIS who underwent EVT from October 2019 to October 2022. Arterial blood was collected every 8 h after EVT to measure PAL, and record the immediate postoperative PAL and the highest PAL level within 24 h. Brain edema was evaluated using brain computed tomography scans within 7 days of EVT. Results: The study included 227 patients with a median age of 71 years, of whom 59.5% were male and MBE developed in 25.6% of patients (58/227). Multivariate logistic regression analysis showed that the immediate postoperative PAL (odds ratio, 1.809 [95% confidence interval (CI), 1.215-2.693]; p = 0.004) and the highest PAL level within 24 h of EVT (odds ratio, 2.259 [95% CI, 1.407-3.629]; p = 0.001) were independently associated with MBE. The area under the curve for predicting MBE based on the highest PAL level within 24 hours of EVT was 0.780 (95% CI, 0.711-0.849). Conclusion: Early increase in PAL levelsis an independent predictor of MBE after EVT in AIS patients.

目的：研究接受血管内治疗（EVT）的急性缺血性卒中（AIS）患者术后恶性脑水肿（MBE）的因素。背景：MBE是EVT治疗AIS后的一种严重并发症，及早识别风险因素至关重要。外周动脉乳酸（PAL）水平可作为 MBE 的潜在预测指标。目的确定术后即刻的 PAL 水平和 EVT 24 小时内的最高 PAL 水平是否与 AIS 患者发生 MBE 独立相关。方法：我们对 AIS 患者进行了回顾性分析：我们回顾性分析了2019年10月至2022年10月期间接受EVT的AIS患者。EVT后每隔8小时采集动脉血以测量PAL，并记录术后即刻的PAL和24小时内的最高PAL水平。研究结果研究共纳入 227 名患者，中位年龄为 71 岁，其中 59.5% 为男性，25.6% 的患者（58/227）出现 MBE。多变量逻辑回归分析显示，术后即刻的 PAL（几率比，1.809 [95% 置信区间 (CI)，1.215-2.693]；p = 0.004）和 EVT 24 小时内的最高 PAL 水平（几率比，2.259 [95% CI，1.407-3.629]；p = 0.001）与 MBE 独立相关。根据 EVT 24 小时内的最高 PAL 水平预测 MBE 的曲线下面积为 0.780（95% CI，0.711-0.849）。结论PAL水平的早期升高是预测AIS患者EVT后MBE的独立指标。

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引用次数: 0

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke 缺血性脑卒中患者的白蛋白-球蛋白比率和颈总动脉内膜厚度

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-12-15 DOI: 10.2174/0115672026276085231122053601

Qiao Han, Shoujiang You, Mengyuan Miao, Danni Zheng, Huaping Du, Yaming Sun, Wanqing Zhai, Chongke Zhong, Yongjun Cao, Chun-Feng Liu

Background: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. background: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in the setting of ischemic stroke are unclear. Methods: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. objective: We aimed to evaluate the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with ischemic stroke. Results: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). Conclusion: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT. result: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was associated with a 59% (OR 0.41; 95% CI 0.29-0.60) decreased risk of having abnormal mean cIMT and 58% (OR 0.42; 95% CI 0.30-0.60) decreased risk of having abnormal maximum cIMT in comparison to Q1, respectively. Moreover, decreased albumin and increased globulin levels were associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided incremental predictive capacity beyond established risk factors, and the C-statistic of A/G ratio for abnormal cIMT is larger than globulin (P<0.01). conclusion: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in patients with ischemic stroke. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT. other: No

背景：急性缺血性卒中（AIS）患者血清白蛋白、白蛋白-球蛋白（A/G）比值、球蛋白与动脉粥样硬化之间的关系仍不确定。我们研究了 AIS 患者血清白蛋白、A/G 比值、球蛋白水平与颈动脉粥样硬化之间的关系：缺血性脑卒中患者血清白蛋白、白蛋白-球蛋白（A/G）比值、球蛋白与动脉粥样硬化之间的关系尚不明确。方法：共纳入 1,339 名 AIS 患者。入院时的 A/G 比值分为四等分，血清白蛋白和球蛋白水平也进行了分类。通过评估颈总动脉内膜中层厚度（cIMT）来检测颈动脉粥样硬化，cIMT 平均值和最大值≥1 毫米为异常。我们使用多变量逻辑回归模型评估了 A/G 比值、白蛋白、球蛋白和异常 cIMT 之间的关系：我们旨在评估缺血性脑卒中患者血清白蛋白、A/G 比值、球蛋白水平与颈动脉粥样硬化之间的关系。结果在多变量调整分析中，A/G 比值最高的四分位数（Q4）与最低的四分位数（Q1）相比，平均 cIMT 异常风险降低了 59%（OR 0.41；95% CI 0.29-0.60），最大 cIMT 异常风险降低了 58%（OR 0.42；95% CI 0.30-0.60）。此外，白蛋白水平降低和球蛋白水平升高也与平均 cIMT 和最大 cIMT 异常有关。此外，A/G 比值在已确定的风险因素之外提供了补充预测能力，A/G 比值对异常 cIMT 的 C 统计量大于球蛋白（P <0.01）。结论血清 A/G 比值降低、白蛋白和血清球蛋白升高与 AIS 患者的 cIMT 异常独立相关。此外，A/G 比值似乎能更好地预测 cIMT 异常：在多变量调整分析中，与 Q1 相比，A/G 比值最高的四分位数（Q4）与平均 cIMT 异常风险降低 59% (OR 0.41; 95% CI 0.29-0.60) 和最大 cIMT 异常风险降低 58% (OR 0.42; 95% CI 0.30-0.60) 相关。此外，白蛋白水平降低和球蛋白水平升高与平均 cIMT 和最大 cIMT 异常有关。此外，A/G 比值的预测能力超过了既有的风险因素，且 A/G比值对异常 cIMT 的 C 统计量大于球蛋白（P<0.01）：缺血性脑卒中患者血清 A/G 比值降低、白蛋白和血清球蛋白升高与 cIMT 异常独立相关。此外，A/G 比值似乎能更好地预测 cIMT 异常：无

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引用次数: 0

Gait Parameters can Reflect Cognitive Performance in Older Adults with Cerebral Small Vessel Disease: A Cross-sectional Research 步态参数可反映患有脑小血管疾病的老年人的认知能力：一项横断面研究

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-12-15 DOI: 10.2174/0115672026281431231212052728

Mingzhu Jiang, Yan Li, Ying Chen, Jinying Fan, Zhiqin Zhao, Wenkai Long, Hailun Huang, Fang Luo, Chao Tang, Mi Li, Ning Xiao, Bo Lin, Shan Wu, Jing Ding

Background: Cerebral small vessel disease (CSVD) is a common chronic progressive disease. It remains unclear whether high gait variability is a marker of cognitive cortical dysfunction. Methods: This study included 285 subjects (aged from 60 to 85 years, 60.3% female) including 37 controls, 179 presented as Fazekas II, and 69 presented as Fazekas III. The severity of white matter hyperintensities was assessed by the Fazekas Rating Scale. Gait parameters were assessed using a vision-based artificial intelligent gait analyzer. Cognitive function was tested by MMSE, MoCA, DST, and VFT. Results: Three gait parameters including gait speed, gait length, and swing time were associated with cognitive performance in patients with CSVD. Gait speed was associated with cognitive performance, including MMSE (β 0.200; 95%CI 1.706-6.018; P <.001), MoCA (β 0.183; 95%CI 2.047-7.046; P <.001), DST (order) (β 0.204; 95%CI 0.563-2.093; P =.001) and VFT (β 0.162; 95%CI 0.753-4.865; P =.008). Gait length was associated with cognitive performance, including MMSE (β 0.193; 95%CI 3.475-12.845; P =.001), MoCA (β 0.213; 95%CI 6.098-16.942; P <.001), DST (order) (β 0.224; 95%CI 1.056-4.839; P <.001) and VFT (β 0.149; 95%CI 1.088- 10.114; P =.015). Swing time was associated with cognitive performance, including MMSE (β - 0.242; 95%CI -2.639 to -0.974; P<.001), MoCA (β -0.211; 95%CI -2.989 to -1.034; P <.001) and DST (reverse order) (β -0.140; 95%CI -0.568 to -0.049; P =.020). Conclusion: This study revealed that the relationship between gait parameters and cognitive performance in patients with CSVD and the deteriorated gait parameters can reflect cognitive impairment and even dementia in older people with CSVD.

背景：脑小血管病（CSVD）是一种常见的慢性进展性疾病。高步态变异性是否是认知皮质功能障碍的标志仍不清楚：本研究共纳入 285 名受试者（年龄在 60 至 85 岁之间，60.3% 为女性），其中包括 37 名对照组受试者、179 名法泽卡斯 II 型受试者和 69 名法泽卡斯 III 型受试者。白质高密度的严重程度通过法泽卡斯分级量表进行评估。步态参数使用基于视觉的人工智能步态分析仪进行评估。认知功能通过 MMSE、MoCA、DST 和 VFT 进行测试：步态速度、步态长度和摆动时间等三个步态参数与 CSVD 患者的认知功能相关。步态速度与认知能力相关，包括 MMSE（β 0.200；95%CI 1.706-6.018；P <；.001）、MoCA（β 0.183；95%CI 2.047-7.046；P <；.001）、DST（阶次）（β 0.204；95%CI 0.563-2.093；P =.001）和 VFT（β 0.162；95%CI 0.753-4.865；P =.008）。步态长度与认知能力有关，包括 MMSE（β 0.193；95%CI 3.475-12.845；P =.001）、MoCA（β 0.213；95%CI 6.098-16.942；P <；.001）、DST（顺序）（β 0.224；95%CI 1.056-4.839；P <；.001）和 VFT（β 0.149；95%CI 1.088-10.114；P =.015）。摇摆时间与认知表现相关，包括 MMSE (β - 0.242; 95%CI -2.639 to -0.974; P <.001)、MoCA (β -0.211; 95%CI -2.989 to -1.034; P <.001)和 DST（逆序）(β -0.140; 95%CI -0.568 to -0.049; P =.020)：本研究揭示了 CSVD 患者步态参数与认知表现之间的关系，步态参数的恶化可反映 CSVD 老年人的认知障碍甚至痴呆。

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引用次数: 0

Association of Cardiac Valve Calcification and 1-year Mortality after Lower-extremity Amputation in Diabetic Patients: A Retrospective Study 糖尿病患者下肢截肢后心脏瓣膜钙化与 1 年死亡率的关系：一项回顾性研究

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-12-12 DOI: 10.2174/0115672026277348231130112221

Weibin Ye, Li Li, Jianfeng Zeng

Background: Cardiac valve calcification predisposes patients to a higher risk of adverse cardiovascular events. This study aimed to investigate the association between cardiac valve calcification and 1-year mortality in diabetic patients after lower-extremity amputation. Methods: This was a retrospective study conducted on the clinical data of diabetic patients who underwent lower-extremity amputation admitted to the Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China for diabetic foot ulcers needed lower extremity amputation surgery between July 2017 and March 2021. Detailed preoperative medical assessments were performed and recorded. Cardiac valve calcification was assessed using echocardiography at baseline. Oneyear follow-up assessments were conducted and included clinical visits, hospital record assessments, and telephone reviews to obtain the survival status of patients. Results: Ninety-three diabetic patients participated in the study. The 1-year follow-up mortality rate after amputation was 24.7%. Compared to the survival group, the prevalence of cardiac valve calcification and the Revised Cardiac Risk Index [RCRI] were higher in the mortality group. In the Cox regression analysis, cardiac valvular calcification [HR=3.427, 95% CI=1.125- 10.443, P=0.030] was found to be an independent predictor of all-cause mortality after amputation. In addition, the patients with both aortic valve calcification and mitral annular calcification had a higher all-cause mortality rate [50%]. Receiver operator characteristic curve analysis showed a stronger predictive ability when using a combination of calcified valve number and RCRI [AUC=0.786 95%, CI=0.676-0.896, P=0.000]. Conclusion: In diabetic patients after lower-extremity amputation, cardiac valve calcification was associated with all-cause mortality during 1-year follow-up. Combination of calcified valve number and RCRI score showed a stronger predictive value for mortality.

背景：心脏瓣膜钙化会增加患者发生不良心血管事件的风险。本研究旨在探讨糖尿病患者下肢截肢后心脏瓣膜钙化与 1 年死亡率之间的关系。研究方法这是一项回顾性研究，研究对象为2017年7月至2021年3月期间因糖尿病足溃疡需行下肢截肢手术而入住中国广东省广州市中山大学孙逸仙纪念医院的糖尿病患者的临床资料。对患者进行了详细的术前医学评估并记录在案。基线时使用超声心动图评估心脏瓣膜钙化情况。进行了一年的随访评估，包括临床访视、医院病历评估和电话回访，以了解患者的生存状况。结果93名糖尿病患者参与了研究。截肢后一年随访死亡率为 24.7%。与存活组相比，死亡组的心脏瓣膜钙化发生率和修正心脏风险指数（RCRI）更高。Cox回归分析发现，心脏瓣膜钙化[HR=3.427，95% CI=1.125-10.443，P=0.030]是截肢后全因死亡率的独立预测因子。此外，主动脉瓣钙化和二尖瓣环钙化患者的全因死亡率更高[50%]。接收者操作特征曲线分析表明，钙化瓣膜数量和 RCRI 的组合预测能力更强[AUC=0.786 95%，CI=0.676-0.896，P=0.000]。结论在下肢截肢后的糖尿病患者中，心脏瓣膜钙化与1年随访期间的全因死亡率相关。钙化瓣膜数量和RCRI评分的组合对死亡率有更高的预测价值。

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引用次数: 0

Ubiquitin-specific protease 8 regulates cognitive dysfunction of mice with sepsis-associated encephalopathy through SIRT1 deubiquitination. 泛素特异性蛋白酶8通过SIRT1去泛素化调节败血症相关脑病小鼠的认知功能障碍。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-07-12 DOI: 10.2174/1567202620666230712112521

Weina Gao, Lijuan Wang, Zuoxiao Li

Background: Sepsis-associated encephalopathy (SAE) is the most severe complication of sepsis. Ubiquitin-specific protease 8 (USP8) could improve cognitive and motor disorders in SAE.

Objective: This study explored the mechanism of USP8 in SAE mice to provide new therapeutic targets for SAE.

Methods: C57BL/6 mice were selected to establish SAE models by caecal ligation and puncture (CLP) and injected with lentivirus overexpressing USP8 one week before SAE modeling. Mouse weight changes were monitored, cognitive and learning abilities were tested by the Morris water maze test, behaviors were evaluated by open-field tests, and pathological changes in brain tissue were analyzed by H&E staining. Levels of USP8, TNF-α, IL-1β, IL-6, and IL-10, and SOD, GSH-Px activities, and MDA levels were detected by Western blot, ELISA, and kits. Co-immunoprecipitation assay verified the interaction between USP8 and SIRT1 and SIRT1 ubiquitination level.

Results: In CLP mice, the body weight, cognitive function, and learning ability were decreased, along with motor disorder, abnormal morphological structure of neurons, and obvious inflammatory infiltration. USP8 protein in brain tissue was decreased, the levels of TNF-α, IL-1β, and IL-6 were increased, IL-10 was decreased, SOD and GSH-Px activities were decreased, and MDA level was increased. USP8 treatment improved cognitive dysfunction and inhibited inflammation and oxidative stress in CLP mice. USP8 promoted SIRT1 expression by direct deubiquitination. SIRT1 knockdown partially reversed the regulation of USP8 on SAE mice.

Conclusion: USP8 can directly deubiquitinate SIRT1 and inhibit inflammatory reactions and oxidative stress, thus improving cognitive dysfunction in SAE mice.

背景:脓毒症相关脑病(SAE)是脓毒症最严重的并发症。泛素特异性蛋白酶8 (USP8)可改善SAE患者的认知和运动障碍。目的:探讨USP8在SAE小鼠中的作用机制，为SAE提供新的治疗靶点。方法:选择C57BL/6小鼠，采用结肠结扎穿刺法(CLP)建立SAE模型，在造模前1周注射过表达USP8的慢病毒。监测小鼠体重变化，Morris水迷宫测试小鼠认知和学习能力，开场实验评估小鼠行为，H&E染色分析小鼠脑组织病理变化。采用Western blot、ELISA和试剂盒检测血清USP8、TNF-α、IL-1β、IL-6、IL-10水平，SOD、GSH-Px活性和MDA水平。免疫共沉淀法证实了USP8与SIRT1的相互作用以及SIRT1泛素化水平。结果:CLP小鼠体重、认知功能、学习能力下降，运动障碍，神经元形态结构异常，炎症浸润明显。脑组织USP8蛋白水平降低，TNF-α、IL-1β、IL-6水平升高，IL-10水平降低，SOD、GSH-Px活性降低，MDA水平升高。USP8治疗改善了CLP小鼠的认知功能障碍，抑制了炎症和氧化应激。USP8通过直接去泛素化促进SIRT1表达。SIRT1敲低部分逆转了USP8对SAE小鼠的调节。结论:USP8可以直接去泛素化SIRT1，抑制炎症反应和氧化应激，从而改善SAE小鼠的认知功能障碍。

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引用次数: 0

Ferroptosis, Iron Metabolism, and Forkhead Transcription Factors (FoxOs). 脱铁症、铁代谢和叉头转录因子（FoxOs）。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-01-01 DOI: 10.2174/1567202620666230706160056

Kenneth Maiese

引用次数: 3

Prevalence and Prognostic Factors of Cortical Laminar Necrosis in Acute Ischemic Stroke. 急性缺血性脑卒中皮质层状坏死的患病率及预后因素分析。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-01-01 DOI: 10.2174/1567202620666230515152331

Zhi-Li Wang, Wei Qin, Yuelei Lyu, Wenli Hu

Background: Cortical laminar necrosis (CLN) is a specific type of cortical infarction, and little is known about its frequency and outcomes. We aimed to investigate the prevalence and outcomes of CLN caused by brain infarction and its prognostic factors.

Methods: This retrospective cohort study included patients with acute ischemic stroke (AIS) between 2019 and 2022 and for whom magnetic resonance images obtained at our center showed acute-stage CLN. Their medical records were collected and analyzed. An unfavorable outcome was defined as a modified Rankin Scale score of 3-6 at 90 days. Logistic regression was performed to identify independent predictors of an unfavorable outcome.

Results: Among 5548 consecutive patients with AIS, 151 patients (2.7%) were diagnosed with CLN, and 112 had CLN enrolled in the final analysis. At 90 days, 25 patients (22.3%) had an unfavorable outcome. Compared with the favorable group, poor outcome patients had higher rates of previous stroke (p = 0.012), higher National Institutes of Health Stroke Scale (NIHSS) scores at admission (p < 0.001), and were more likely to have early neurologic deterioration (END) (p = 0.014), diffuse ischemic lesions (p = 0.011), and lesions involving multiple lobes (p = 0.030). In multivariable analysis, the initial NIHSS score (OR, 1.258, (95% CI 1.090 - 1.453), p = 0.002) and END (OR, 5.695, [95% CI 1.410 - 23.007], p = 0.015) were independently associated with unfavorable outcome.

Conclusion: CLN is a rare ischemic event but has a good prognosis in most cases. A higher initial NIHSS score and END may predict an unfavorable outcome.

背景:皮质层状坏死(CLN)是一种特殊类型的皮质梗死，其发病率和预后知之甚少。我们的目的是调查脑梗死引起的CLN的患病率和预后及其预后因素。方法:本回顾性队列研究纳入2019年至2022年间急性缺血性脑卒中(AIS)患者，这些患者在本中心获得的磁共振图像显示为急性期CLN。他们的医疗记录被收集和分析。不良结果定义为90天时改良Rankin量表得分为3-6分。进行逻辑回归以确定不利结果的独立预测因素。结果:在5548例连续AIS患者中，151例(2.7%)被诊断为CLN，最终分析中有112例患有CLN。在90天，25例患者(22.3%)出现不良结果。与预后良好组相比，预后差的患者既往卒中发生率更高(p = 0.012)，入院时美国国立卫生研究院卒中量表(NIHSS)评分更高(p < 0.001)，更有可能出现早期神经系统恶化(END) (p = 0.014)、弥漫性缺血性病变(p = 0.011)和多叶病变(p = 0.030)。在多变量分析中，初始NIHSS评分(OR, 1.258， (95% CI 1.090 - 1.453)， p = 0.002)和END (OR, 5.695， [95% CI 1.410 - 23.007]， p = 0.015)与不良结局独立相关。结论:CLN是一种罕见的缺血性事件，但大多数病例预后良好。较高的初始NIHSS评分和END可能预示不利的结果。

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引用次数: 0

DDX3X Deficiency Attenuates Pyroptosis Induced by Oxygen-glucose Deprivation/Reoxygenation in N2a Cells. DDX3X缺乏可减弱N2a细胞氧-葡萄糖剥夺/再氧化诱导的焦亡。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-01-01 DOI: 10.2174/1567202620666230522155944

Yong Liu, Yanlin Gui, Hao Tang, Jianping Yu, Zhengzhou Yuan, Lei Liu, Xuntai Ma, Changqing Li

Background: NOD like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis is strongly related to cerebral ischemia/reperfusion (I/R) injury. DDX3X, the DEAD-box family's ATPase/RNA helicase, promotes NLRP3 inflammasome activation. However, whether DDX3X deficiency attenuates NLRP3 inflammasome-mediated pyroptosis induced by cerebral I/R injury.

Objectives: This study investigated whether DDX3X deficiency attenuates NLRP3 inflammasomemediated pyroptosis in N2a cells after oxygen-glucose deprivation/ reoxygenation (OGD/R) treatment.

Methods: In vitro model of cerebral I/R injury, mouse neuro2a (N2a) cells subjected to OGD/R were treated with the knockdown of DDX3X. Cell counting kit-8 (CCK-8) assay and Lactate dehydrogenase (LDH) cytotoxicity assay were conducted to measure cell viability and membrane permeability. Double immunofluorescence was performed to determine the pyroptotic cells. Transmission electron microscopy (TEM) was used to observe morphological changes of pyroptosis. Pyroptosis-associated proteins were analyzed by Western blotting.

Results: The OGD/R treatment reduced cell viability, increased pyroptotic cells and released LDH compared to the control group. TEM showed membrane pore formation of pyroptosis. Immunofluorescence showed that GSDMD was translocated from the cytoplasm to the membrane after OGD/R treatment. Western blotting showed that the expression of DDX3X, and pyroptosis-related proteins (NLRP3, cleaved-Caspase1, and GSDMD-N) were increased after OGD/R treatment. Nevertheless, DDX3X knockdown markedly improved cell viability and reduced LDH release, expression of pyroptosis-related proteins, and N2a cells pyroptosis. DDX3X knockdown significantly inhibited membrane pore formation and GSDMD translocation from cytoplasm to membrane.

Conclusion: This research demonstrates for the first time that DDX3X knockdown attenuates OGD/R induced NLRP3 inflammasome activation and pyroptosis, which implies that DDX3X may become a potential therapeutic target for cerebral I/R injury.

背景:NOD样受体蛋白3 (NLRP3)炎症小体介导的焦亡与脑缺血/再灌注(I/R)损伤密切相关。DEAD-box家族的atp酶/RNA解旋酶DDX3X促进NLRP3炎性体的激活。然而，DDX3X缺乏是否减弱脑I/R损伤诱导的NLRP3炎症小体介导的焦亡。目的:本研究探讨DDX3X缺乏是否能减轻氧-糖剥夺/再氧化(OGD/R)治疗后N2a细胞NLRP3炎症介导的焦凋亡。方法:在体外建立脑I/R损伤模型，通过敲低DDX3X处理OGD/R损伤小鼠神经2a (N2a)细胞。采用细胞计数试剂盒-8 (CCK-8)法和乳酸脱氢酶(LDH)细胞毒性法测定细胞活力和细胞膜通透性。双免疫荧光法测定热噬细胞。透射电镜(TEM)观察焦亡的形态学变化。Western blotting分析热释热相关蛋白。结果:与对照组相比，OGD/R处理降低了细胞活力，增加了焦亡细胞，释放了LDH。透射电镜显示焦亡形成膜孔。免疫荧光显示，经OGD/R处理后，GSDMD从细胞质转移到膜上。Western blotting结果显示，OGD/R处理后，DDX3X、NLRP3、cleaved-Caspase1、GSDMD-N等相关蛋白表达增加。然而，DDX3X敲低显著提高了细胞活力，降低了LDH的释放，降低了焦亡相关蛋白的表达，减少了N2a细胞的焦亡。DDX3X基因敲低显著抑制膜孔形成和GSDMD从细胞质向膜的易位。结论:本研究首次证实DDX3X基因敲低可减轻OGD/R诱导的NLRP3炎性体激活和焦亡，提示DDX3X可能成为脑I/R损伤的潜在治疗靶点。

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引用次数: 1

Effects of Different Etiologies of Anterior Circulation Tandem Lesions on Short-term Prognosis of Acute Ischemic Stroke. 前循环串联病变不同病因对急性缺血性脑卒中短期预后的影响。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-01-01 DOI: 10.2174/1567202620666230201121411

Zhichao Huang, Yingying Xu, Shoujiang You, Zhiliang Guo, Jiaping Xu, Yongjun Cao, Guodong Xiao, Chun-Feng Liu

Introduction: The prognosis of anterior circulation tandem lesions caused by carotid artery dissection (CAD) and large artery atherosclerosis (LAA) after mechanical thrombectomy is controversial. By analyzing the clinical data of different etiologies, we explored the best treatment plan.

Methods: Clinical data of patients with anterior circulation tandem lesions admitted to the Second Affiliated Hospital of Soochow University from April 2018 to October 2021 were retrospectively collected. The Modified Rankin Scale was used as the standard to evaluate the functional prognosis of patients at 3 months. Safety assessment included symptomatic intracranial hemorrhage (sICH) and mortality. The technical evaluation of interventional procedures included operation time, successful recanalization, and times of pass.

Results: 74 patients were enrolled, 59 in the LAA group and 15 in the CAD group. The two groups were similar regarding the proportion of successful recanalization, the bridge treatment and the choice of surgical instruments. The puncture to recanalization time and the onset of symptoms to successful recanalization time had no significant difference (p > 0.05). There were no significant differences in hemorrhage transformation (p = 0.26), sICH (p > 0.999), good functional prognosis (p = 0.054), and mortality (p = 0.181) between the two groups. We found a trend toward a better functional outcome at 3 months in the CAD group (p = 0.054).

Conclusion: The tandem lesions of anterior circulation caused by CAD tend to have a good functional prognosis in 3 months. The proportion of successful recanalization and surgical safety was similar between the two groups.

导论:机械取栓后颈动脉夹层(CAD)和大动脉粥样硬化(LAA)所致前循环串联病变的预后存在争议。通过分析不同病因的临床资料，探讨最佳治疗方案。方法:回顾性收集2018年4月至2021年10月东吴大学附属第二医院收治的前循环串联病变患者的临床资料。采用改良Rankin量表作为评价患者3个月功能预后的标准。安全性评估包括症状性颅内出血(siich)和死亡率。介入手术的技术评价包括手术时间、成功再通和通过次数。结果:74例患者入组，其中LAA组59例，CAD组15例。两组在再通成功率、桥接治疗和手术器械选择方面相似。穿刺至再通时间、出现症状至再通成功时间差异无统计学意义(p > 0.05)。两组在出血转化(p = 0.26)、脑出血(p > 0.999)、功能预后良好(p = 0.054)、病死率(p = 0.181)方面差异均无统计学意义。我们发现CAD组在3个月时有更好的功能结局的趋势(p = 0.054)。结论:冠心病致前循环串联病变3个月功能预后良好。两组再通成功率和手术安全性相似。

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引用次数: 0

Valsartan Protects in High Fat Diet During Ischemic Reperfusion Injury. 缬沙坦对高脂肪饮食缺血性再灌注损伤的保护作用。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current neurovascular research

Pub Date : 2023-01-01 DOI: 10.2174/1567202620666230330084654

Simrat Kaur, Kuldeep Kumar, Nirmal Singh, Amteshwar Singh Jaggi

Aim: The study investigates the effect of Valsartan, an Angiotensin II type 1 receptor blocker (ARB), on the blunted neuroprotective response of ischemic post-conditioning (iPoCo) in rats subjected to High Fat Diet (HFD).

Background: The neuroprotective response of iPoCo is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolemia, diabetes, hypertension, etc. Objectives: The study was undertaken to investigate the effect of Valsartan, an ARB, on the blunted neuroprotective response of iPoCo in rats subjected to HFD.

Methods: Wistar rats were subjected to HFD for 56 days. The cerebral ischemic injury was induced by bilateral common carotid artery occlusion (BCCAO) for 12 min followed by reperfusion of 24 hrs. iPoCo was induced by three preceding cycles of ischemia and reperfusion lasting 1 min each given immediately after BCCAO at the onset of prolonged reperfusion. The extent of the injury was assessed in terms of memory impairment using the Morris Water Maze test (MWM), sensorimotor disturbance using the neurological severity score (NSS), and cerebral infarct size using triphenyl tetrazolium chloride staining. Series of biochemical estimations including brain thiobarbituric acid reactive species (TBARS); reduced glutathione (GSH); myeloperoxidase (MPO); tumor necrosis factor-α (TNF-α); Nrf-2 and serum cholesterol, serum nitrite levels were performed.

Results: BCCAO produced significant cerebral injury indicated by increased cerebral infarct size, memory impairment, increased NSS, and various biochemical alterations (increased cholesterol, TBARS, MPO, TNF-α, Nrf-2, and decreased nitrite and GSH levels). Significant neutrophil infiltration was also observed. iPoCo attenuated BCCAO-induced injury with respect to the above parameters in normal rats. The protective response of iPoCo was lost in HFD-treated rats. Treatment of Valsartan attenuated cerebral injury, potentiated the neuroprotective response of iPoCo in normal rats, and also restored the blunted neuroprotective effect of iPoCo in HFD-treated rats along with enhanced Nrf-2 levels.

Conclusion: Valsartan exerted a neuroprotective effect by virtue of its multiple actions with a crucial role of Nrf2 activation.

目的:研究血管紧张素II型受体阻滞剂缬沙坦(ARB)对高脂饮食大鼠缺血后适应(iPoCo)神经保护反应钝化的影响。背景:在与高胆固醇血症、糖尿病、高血压等相关的血管内皮功能障碍(ED)患者中，iPoCo的神经保护作用减弱。目的:研究缬沙坦(ARB)对HFD大鼠iPoCo神经保护反应减弱的影响。方法:Wistar大鼠灌胃56 d。双侧颈总动脉闭塞(BCCAO) 12 min后再灌注24 h诱导脑缺血损伤。iPoCo是在延长再灌注开始时，BCCAO后立即进行三个缺血再灌注周期，每个周期持续1分钟。使用Morris水迷宫测试(MWM)评估损伤程度，使用神经严重程度评分(NSS)评估感觉运动障碍，使用三苯四唑氯染色评估脑梗死面积。包括脑硫代巴比妥酸反应物质(TBARS)在内的一系列生化评价;还原性谷胱甘肽(GSH);髓过氧化酶(MPO);肿瘤坏死因子-α (TNF-α);测定Nrf-2、血清胆固醇、亚硝酸盐水平。结果:BCCAO造成明显的脑损伤，表现为脑梗死面积增加、记忆障碍、NSS增加和各种生化改变(胆固醇、TBARS、MPO、TNF-α、Nrf-2增加，亚硝酸盐和GSH水平降低)。同时观察到明显的中性粒细胞浸润。与上述参数相比，iPoCo对正常大鼠bccao诱导的损伤有减弱作用。iPoCo的保护作用在hfd处理的大鼠中消失。缬沙坦治疗可减轻脑损伤，增强正常大鼠iPoCo的神经保护反应，并恢复hfd治疗大鼠iPoCo的减弱神经保护作用，同时提高Nrf-2水平。结论:缬沙坦具有多重作用的神经保护作用，其中Nrf2激活起着至关重要的作用。

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引用次数: 0