硫化氢对抗脑缺血再灌注损伤的机制研究进展

硫化氢（H2S）是一种新型内源性气体信使分子,在许多生理和病理生理过程中,尤其在神经保护中,扮演重要角色,既是神经调节剂, 也是神经保护剂。近年来的研究发现,H2S对于脑缺血再灌注损伤具有积极的防治作用,它可通过抗氧化应激、抗炎及抗细胞凋亡等多个途径, 对脑缺血再灌注损伤起保护作用,具有良好的临床应用前景。简介脑内H2S生成途径,综述H2S在中枢神经系统中的生物学效应及其对脑 缺血再灌注损伤的保护作用与机制研究进展,以期为脑缺血再灌注损伤的临床防治提供新思路。     

血清胱抑素C、血肌酐及血尿素氮对窒息新生儿肾功能损害的临床意义

目的:探讨体外反搏联合言语训练治疗脑性瘫痪并语言发育迟缓儿童的临床疗效。方法:选择2015年12月至2017年12月在上海市儿童医院康复科普通门诊确诊的脑瘫并语言发育迟缓患儿52例,按照随机数字表法将其随机分为治疗组和对照组,每组26例。对照组仅给予言语训练治疗,治疗组给予体外反搏联合言语训练治,以4周1个疗程,两组均治疗3个疗程。治疗前后,采用中国康复研究中心汉语版儿童语言发育评定法s-s法、Gesell发育评分法评价和比较患儿言语发育商和认知发育商的变化。结果:治疗后,两组言语发育商和认知发育商均显著高于治疗前,且治疗组言语发育商和认知发育商均显著高于对照组,差异均有统计学意义(均P0.01)。结论:体外反搏联合言语训练较单纯言语训练可更有效改善脑瘫并语言发育迟缓患儿的言语发育和认知发育。     

颈动脉斑块LRNC特征可诊断2型糖尿病患者急性脑梗死的风险

2型糖尿病可能加重颈动脉斑块的易损性并增加缺血性中风的风险,关于2型糖尿病患者伴有颈动脉斑块特征的急性中风亚型鲜有研究报道。本研究旨在探讨2型糖尿病患者颈动脉斑块特征与MRI确定的急性脑梗死病变特征之间的关系。本研究以颈内动脉区急性脑血管病患者为研究对象,所有患者分为2型糖尿病组和非2型糖尿病组,分别行颈动脉和脑部MRI扫描,测定同侧颈动脉斑块的形态和特征,以及颅内和颅外颈动脉狭窄。基于中风亚型和急性脑梗塞病变模式对患者进行评估。研究结果表明,与非2型糖尿病患者相比,2型糖尿病患者颈动脉型IV-VI病变的患病率更高,斑块负荷更大,以及富脂质坏死核(LRNC)更大。在有症状的颈动脉LRNC患者中,与非2型糖尿病组相比,2型糖尿病组颈内动脉区出现较多的伴有大穿孔动脉梗塞形态和较大的急性脑梗塞。LRNC%>23.5%的颈动脉斑块是2型糖尿病患者存在颈动脉狭窄的急性脑梗塞病变的独立危险因素。颈动脉斑块特征的量化,尤其是MRI诊断的富脂质坏死核对中风风险具有潜在应用价值。     

β‐arrestin 2 negatively regulates NOD2 signalling pathway through association with TRAF6 in microglia after cerebral ischaemia/reperfusion injury

We previously reported that nucleotide‐binding oligomerization domain‐containing protein (NOD) 2 was involved in the inflammatory responses to cerebral ischaemia/reperfusion (I/R) insult. However, the mechanism by which NOD2 participates in brain ischaemic injury and the regulation of NOD2 in the process are still obscure. Increased β‐arrestin 2 (ARRB2) expression was observed in microglia following cerebral I/R in wild‐type mice besides the up‐regulation of NOD2 and TRAF6. Stimulation of NOD2 by muramyl dipeptide (MDP) in BV2 cells induced the activation of NF‐κB by the phosphorylation of p65 subunit and the degradation of IκBα. Meanwhile, the protein level of Cyclooxygenase‐2 (COX‐2), the protein expression and activity of MMP‐9 were significantly increased in BV2 cells after administration of MDP. Furthermore, overexpression of ARRB2 significantly suppressed the inflammation induced by MDP, silence of ARRB2 significantly enhanced the inflammation induced by MDP in BV2 cells. In addition, we observed endogenous interaction of TRAF6 and ARRB2 after stimulation of MDP or cerebral I/R insult, indicating ARRB2 negatively regulates NOD2‐triggered inflammatory signalling pathway by associating with TRAF6 in microglia after cerebral I/R injury. Finally, the in vivo study clearly confirmed that ARRB2 negatively regulated NOD2‐induced inflammatory response, as ARRB2 deficiency exacerbated stroke outcomes and aggravated the NF‐κB signalling pathway induced by NOD2 stimulation after cerebral I/R injury. These findings revealed ARRB2 negatively regulated NOD2 signalling pathway through the association with TRAF6 in cerebral I/R injury.     

Decreased cerebral blood flow and hemodynamic parameters during acute hyperglycemia in mice model observed by dual‐wavelength speckle imaging

In this study, we use dual‐wavelength optical imaging‐based laser speckle technique to assess cerebral blood flow and metabolic parameters in a mouse model of acute hyperglycemia (high blood glucose). The effect of acute glucose levels on physiological processes has been extensively described in multiple organ systems such as retina, kidney, and others. We postulated that hyperglycemia also alters brain function, which in turn can be monitored optically using dual‐wavelength laser speckle imaging (DW‐LSI) platform. DW‐LSI is a wide‐field, noncontact optical imaging modality that integrates the principles of laser flowmetry and oximetry to obtain macroscopic information such as hemoglobin concentration and blood flow. A total of eight mice (C57/BL6) were used, randomized into two groups of normoglycemia (control, n = 3) and hyperglycemia (n = 5). Hyperglycemia was induced by intraperitoneal injection of a commonly used anesthetic drug combining ketamine and xylazine (KX combo). We found that this KX combo increases blood glucose (BG) levels from 150 to 350 mg/dL, approximately, when measured 18 minutes post‐administration. BG continues to increase throughout the test period, with BG reaching an average of 463 ± 20.34 mg/dL within 60 minutes. BG levels were measured every 10 minutes from tail blood using commercially available glucometer. Experimental results demonstrated reductions in cerebral blood flow (CBF) by 55%, tissue oxygen saturation (SO₂) by 15%, and cerebral metabolic rate of oxygen (CMRO₂) by 75% following acute hyperglycemia. The observed decrease in these parameters was consistent with results reported in the literature, measured by a variety of experimental techniques. Measurements with laser Doppler flowmetry (LDF) were also performed which confirmed a reduction in CBF following acute hyperglycemia. In summary, our findings indicate that acute hyperglycemia modified brain hemodynamic response and induced significant changes in blood flow and metabolism. As far as we are aware, the implementation of the DW‐LSI to monitor brain hemodynamic and metabolic response to acute hyperglycemia in intact mouse brain has not been previously reported.      

Dynamic imaging and quantification of subcellular motion with eigen‐decomposition optical coherence tomography‐based variance analysis

The dynamic properties of subcellular organism are important biomarkers of the health. Imaging subcellular level dynamics provides effective solutions for evaluating cell metabolism and testing the responses of cells to pathogens and drugs in pharmaceutical engineering. In this paper, we demonstrate an innovative approach to contrast the subcellular motion by using eigen decomposition (ED)‐based variance analysis of time‐dependent complex optical coherence tomography signals. This method reveals a superior advantage of contrast to noise ratio when compared with the approach that employs intensity decorrelation. Furthermore, the eigen values derived from ED processing are calculated and applied to assess the power ratios of complex signal invariance that decreases exponentially along time dimension. The validation experiments are performed on the patterned samples of yeast powder mixed with gelatin/TiO2 water solution. Additionally, the proposed method is used to image mouse cerebral cortex in normal and pathological conditions, suggesting the practicality of variance power mapping in analyzing cortical neural activities. The technique promises efficient measurement of subcellular motions with high sensitivity and high throughput for in vivo and in situ applications.     

Modeling Patient-Derived Glioblastoma with Cerebral Organoids

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头针对局灶性脑缺血脑微血管内皮细胞ICAM-1影响的动态观察

目的:在分子水平探讨并阐明脑缺血再灌注脑损伤的炎性机理和针刺对局灶性脑缺血模型脑微血管内皮细胞功能的动态影响。方法:采用大脑中动脉线栓阻塞法建立大鼠局灶性脑缺血模型;用免疫组化SABC法检测脑缺血后治疗1d、3d、5d、10d细胞间粘附分子-1的表达。结果:针刺不同疗程治疗各组大鼠在治疗前后的神经症状行为评定分析有显著性差异(p＜0．05);模型组ICAM-1脑缺血后ID即出现表达,5D达到表达高峰,各个时间点相比具有显著的统计学意义(P＜0．01)。结论:头针对脑缺血状态下微血管内皮细胞功能的全方位和多层面良性调节机制,并且这种良性机制随着干预时间的选择(早期/6 d)和疗程的适度延长(5天以上),具有明显的累加蓄积效应。     

芪蝎活血通络汤对局灶性脑缺血再灌注损伤模型大鼠神经功能、氧化应激及炎症因子的影响

目的:探讨芪蝎活血通络汤对局灶性脑缺血再灌注损伤模型大鼠神经功能、氧化应激及炎症因子的影响。方法:50只SD大鼠随机选取40只采用线栓法构建脑缺血再灌注模型,其中36只成功,4只死亡。随机数字表法将36只脑缺血再灌注模型大鼠分为模型组、低剂量组(芪蝎活血通络汤2.0 mg/kg灌胃处理)、中剂量组(芪蝎活血通络汤4.0 mg/kg灌胃处理)和高剂量组(芪蝎活血通络汤8.0 mg/kg灌胃处理),每组9只,剩余10只大鼠仅切开皮肤分离和夹闭血管(对照组)。建模后芪蝎活血通络汤各剂量组给予相应剂量灌胃,对照组和模型组给予同剂量生理盐水灌胃,持续4周。用药4周后测评各组大鼠神经功能缺损程度、双侧贴纸去除时间、平衡木过杆时间,并测定各组大鼠脑组织中含水量、脑梗死面积以及氧化应激[过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)]和炎症因子[白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)]指标。结果:与对照组比较,模型组大鼠m NSS评分、脑组织含水量、MDA含量、IL-6、IL-1β、TNF-α水平升高(P<0.05),双侧贴纸去除时间、平衡木过杆时间延长(P<0.05),脑梗死面积增大(P<0.05),SOD、GSH-Px、CAT活性降低(P<0.05);与模型组比较,芪蝎活血通络汤各剂量组大鼠m NSS评分、脑组织含水量、MDA含量、IL-6、IL-1β、TNF-α水平降低(P<0.05),双侧贴纸去除时间、平衡木过杆时间缩短(P<0.05),脑梗死面积缩小(P<0.05),SOD、GSH-Px、CAT活性升高(P<0.05);与低剂量组比较,中、高剂量组大鼠m NSS评分降低(P<0.05),双侧贴纸去除时间、平衡木过杆时间缩短(P<0.05);高剂量组大鼠脑梗死面积、脑组织MDA、IL-6、IL-1β、TNF-α低于低剂量组(P<0.05),SOD、GSH-Px、CAT高于低剂量组(P<0.05)。结论:芪蝎活血通络汤可降低大鼠脑缺血再灌注损伤,改善神经功能,其治疗作用可能与抗氧化,抗炎作用有关,8.0 mg/kg剂量效果最显著。     

西洛他唑在急性脑梗死患者rt-PA溶栓治疗后的作用及对血清CD62p、CD63、PAF的作用分析

摘要 目的：探讨西洛他唑在急性脑梗死患者重组人组织型纤溶酶原激活物（rt-PA）溶栓治疗后的作用及对血清血小板溶酶体膜蛋白（CD63）、α颗粒膜糖蛋白（CD62p）、血小板活化因子（PAF）的作用分析。方法：选择2020年2月至2022年2月我院接诊的90例急性脑梗死患者,按照随机数表法分为观察组及对照组,各45例。两组均接受rt-PA溶栓治疗,对照组溶栓后使用阿司匹林治疗,观察组在对照组基础上,联合西洛他唑治疗,均连续治疗14 d。比较两组临床疗效、血清CD62p、CD63、PAF、全血粘度、血浆粘度和红细胞比容（HCT）及美国国立卫生院卒中量表（NIHSS）评分、巴氏量表（Barthel指数）评分的变化及出血事件发生率。结果：观察组患者的临床疗效总有效率为91.11%,高于对照组的73.33%,有统计学意义（P＜0.05）;观察组血清CD62p、CD63、PAF均比对照组低,有统计学意义（P＜0.05）;观察组全血粘度、血浆粘度、HCT均比对照组低,有统计学意义（P＜0.05）;观察组的NIHSS评分均低于对照组,Barthel指数高于对照组,有统计学意义（P＜0.05）;两组出血事件总发生率比较,无统计学意义（P＞0.05）。结论：西洛他唑在急性脑梗死患者rt-PA溶栓治疗后的作用明显,可有效降低血清CD62p、CD63、PAF的表达,改善血小板功能,安全性较好,值得临床推广。