Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.     

Mechanisms of Hyperhomocysteinemia Induced Skeletal Muscle Myopathy after Ischemia in the CBS?/+ Mouse Model

Although hyperhomocysteinemia (HHcy) elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy) metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR) that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE) make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS^−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy) or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Identification and Functional Analysis of MicroRNAs in Mice following Focal Cerebral Ischemia Injury

Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs) are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims of this study were to quantify the altered expression levels of miRNAs in the infarct region 6 h after middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in mice using a large-scale miRNAs microarray. Firstly, MCAO-induced cerebral ischemic injuries were investigated by observing the changes of neurological deficits, infarct volume and edema ratio. One hundred and eighteen differentially expressed miRNAs were identified in the infarct region of mice following the MCAOs compared with sham group (p < 0.05 was considered as significant). Among these 118 significantly expressed microRNAs, we found that 12 miRNAs were up-regulated with fold changes lager than two, and 18 miRNAs were down-regulated with fold changes less than 0.5 in the infarct region of mice following the 6 h MCAOs, compared with the sham group. Then, these 30 miRNAs with expression in fold change larger than two or less than 0.5 was predicted, and the functions of the target genes of 30 miRNAs were analyzed using a bioinformatics method. Finally, the miRNA-gene network was established and the functional miRNA-mRNA pairs were identified, which provided insight into the roles of the specific miRNAs that regulated specified genes in the ischemic injuries. The miRNAs identified in this study may represent effective therapeutic targets for stroke, and further study of the role of these targets may increase our understanding of the mechanisms underlying ischemic injuries.     

汽车驾驶员脑氧参数的振动响应特性分析

应用近红外光谱法,研究分析汽车驾驶员在振动状态下的脑部血氧参数变化,探讨车辆振动对脑氧参数的影响。实验过程中应用近红外光谱法监测试验人员脑氧参数。经方差分析发现实验人员经车辆振动后脑部各血氧参数有显著性变化。实验结果表明汽车振动对脑部血氧参数还原血红蛋白的浓度(c_Hb)、氧合血红蛋白的浓度(c_HbO2)、血红蛋白总量的浓度(c_tHb)有显著性影响,且不同频率振动的影响显著性不同,其中4.5Hz的振动对脑氧参数影响最大;但振动对脑部组织血氧饱和度(tissue oxygen index,TOI)的影响极小。     

基于精细解剖结构的左心室心肌缺血仿真

为解释心肌缺血诱发心律失常的机理,基于精细的人体心脏解剖数据,构建了一个整合的人体心室组织模型,并模拟了心肌缺血对折返波的影响.在处理无通量边界问题上,采用相场法来自动处理复杂的边界条件.通过增加缺血区域内细胞外钾离子浓度值,模拟了心肌缺血环境下折返波的传播过程.实验结果表明,折返波会随着缺血程度的改变而变化.随着缺血...     

实验大鼠脑缺血模型的制作及效果评价

缺血性脑血管病是临床上常见的一类疾病，其致残率和死亡率均较高。采用一种线栓法，制备大鼠局灶性脑缺血再灌注模型，并从动物神经病学评分、鼠脑整体观、鼠脑切面氯化三苯四氮唑染色、鼠脑组织光镜下观察等进行评价，表明该模型达到脑缺血的效果。在此基础上可进行缺血性脑血管病的多种实验性研究。     

脑血栓康复训练器的机械结构设计

为提高我国脑血栓患者的康复效率,减轻护理强度,设计了一种针对脑血栓患者的康复训练机器人。该康复训练机器人可协助患者在站立姿态和坐姿之间切换,坐姿状态下,康复训练机器人可实现电动轮椅的功能,在站立姿态下可利用仿生外骨骼装置辅助患者进行行走训练。     

坐姿下人体振动特性建模及实验分析

为客观评价垂直振动条件下人体生物力学响应,依据多体动力学原理建立了七自由度无靠背坐姿下人体振动模型。根据不同频率下人体振动实验数据,采用最小二乘参数识别法以及加权计算得到人体动力学参数,根据识别出的参数进行人体振动特性分析,得到了特定频率下人体头部振动加速度响应特性。应用近红外光谱法无创检测脑部组织血氧参量,分析了不同频率下血氧参数变化。实验结果表明:该模型有较高的预测精度,可为动态环境下人机界面设计提供重要参考,对于客观评价人体坐姿舒适性,提高汽车人机界面设计宜人性有指导意义。     

Inspection time and attention-deficit/hyperactivity disorder symptoms in children with cerebral palsy.

Objective: To examine between-groups differences in the associations between aspects of processing speed assessed with an inspection time task and attention-deficit/hyperactivity disorder (ADHD) symptoms. Research Design: Two groups comprising 34 children with cerebral palsy (CP) and 70 nonaffected peers (control), ages 8–16 years, participated in a prospective correlational study. Measures included a visual inspection time task and the Conners' Parent Rating Scale—Revised: Long Version. Results: Children with CP exhibited significantly slower processing speed and more symptoms of inattention and hyperactivity than controls. Significant associations between inspection time and ADHD symptoms were found only in the control group. Conclusions: Findings have implications for clinical assessment and understanding of attentional risks associated with CP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)