Tianen Zhou

Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines

OBJECTIVE The latest guidelines both increased the requirements of chest compression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality chest compression. In this study, we investigated the quality of chest compressions during compression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue. METHODS Eighty-six undergraduate volunteers were randomly assigned to perform CPR according to the 2005 AHA guidelines (AHA 2005) or AHA 2010. After the training course and theoretical examination of basic life support, eight min of compression-only CPR performance was assessed. The quality of chest compressions including rate and depth of compression was analyzed. The rescuer fatigue was evaluated by the changes of heart rate and blood lactate, and rating of perceived exertion. RESULTS Thirty-nine participants in the AHA 2005 group and 42 participants in the AHA 2010 group completed the study. Significantly greater mean chest compression depth and compression rate were both achieved in the AHA 2010 group than in the AHA 2005 group. And significantly greater rescuer fatigue was observed in the AHA 2010 group. In addition, the female in the AHA 2010 group could perform the compression rate required by the guidelines, however, significantly shallower compression depth and greater rescuer fatigue were observed when compared to the male. CONCLUSIONS The quality of chest compressions was significantly improved following the 2010 AHA guidelines, however, its more difficult for the rescuer to meet the guidelines due to the increased fatigue of rescuer.

Protective effect of mild hypothermia on oxygen-glucose deprivation injury in rat hippocampal neurons after hypoxia

The present study aimed to establish an oxygen‑glucose deprivation (OGD) model of ischemic and hypoxic cerebral neurons to investigate the protective effect of mild hypothermia on neuronal OGD and its mechanisms. OGD injury was significantly mitigated in cells with 24 h of mild hypothermia compared with cells without mild hypothermia; cell morphology improved, the lactic acid dehydrogenase (LDH) release rate was decreased, cytoactivity was increased and the neuronal apoptotic rate was decreased. By contrast, no significant improvement in injury was observed after 6 h of mild hypothermia. This suggests that mild hypothermia treatment following OGD is effective only when implemented for 24 h. Additionally, the caspase-3 activity of neurons increased following OGD, which was positively associated with the neuronal apoptotic rate. However, the caspase-3 activity after 24 h of mild hypothermia was reduced. Simultaneously, the neuronal apoptotic rate was decreased, suggesting that mild hypothermia may inhibit neuronal apoptosis by reducing caspase-3 activity. Therefore, reducing caspase-3 activity potentially constitutes one of the protective mechanisms of mild hypothermia in neuronal OGD.

Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux

ABSTRACT Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen‐glucose deprivation/reperfusion(OGD/R)‐induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP‐GFP tf‐LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up‐regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R‐induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R‐induced injury by improving lysosomal function and autophagic flux. HIGHLIGHTSOGD/R impaires lysosomes and impedes the autophagic flux in hippocampal neurons.Mild hypothermia rescues lysosomal function in neurons following OGD/R.Mild hypothermia up‐regulates the autophagic flux in neurons following OGD/R.Mild hypothermia improves mitochondrial autophagy in neurons following OGD/R.Chloroquine blocks the protective effects of mild hypothermia against OGD/R injury.

Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons

Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.

Microarray analysis of an synthetic α-synuclein induced cellular model reveals the expression profile of long non-coding RNA in Parkinson’s disease

Long non-coding RNAs (lncRNAs) are a new research focus that are reported to influence the pathogenetic process of neurodegenerative disorders. To uncover new disease-associated genes and their relevant mechanisms, we carried out a gene microarray analysis based on a Parkinsons disease (PD) in vitro model induced by α-synuclein oligomers. This cellular model induced by 25 μmol/L α-synuclein oligomers has been confirmed to show the stable, transmissible neurotoxicity of α-synuclein, a typical PD pathological marker. And several differentially expressed lncRNAs and mRNAs were identified in this model, such as G046036, G030771, AC009365.4, RPS14P3, CTB-11I22.1, and G007549. Subsequent ceRNA analysis determined the potential relationships between these lncRNAs and their associated mRNAs and microRNAs. The results of the present study widen our horizon of PD susceptibility genes and provide new pathways towards efficient diagnostic biomarkers and therapeutic targets for PD.

Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway

In addition to its original application for treating tuberculosis, rifampicin has multiple potential neuroprotective effects in chronic neurodegenerative diseases including Parkinson’s disease (PD) and Alzheimer’s disease. Inflammatory reactions and the PI3K/Akt pathway are strongly implicated in dopaminergic neuronal death in PD. This study aims to investigate whether rifampicin protects rotenone-lesioned SH-SY5Y cells via regulating PI3K/Akt/GSK-3β/CREB pathway. Rotenone-treated SH-SY5Y cells were used as the cell model to investigate the neuroprotective effects of rifampicin. Cell viability and apoptosis of SH-SY5Y cells were determined by CCK-8 assay and flow cytometry, respectively. The expression of Akt, p-Akt, GSK-3β, p-GSK-3β, CREB and p-CREB were measured by Western blot. Our results showed that the cell viability and level of phospho-CREB significantly decreased in SH-SY5Y cells exposed to rotenone when compared to the control group. Both the cell viability and the expression of phospho-CREB in cells pretreated with rifampicin were higher than those of cells exposed to rotenone alone. Moreover, pretreatment of SH-SY5Y cells with rifampicin enhanced phosphorylation of Akt and suppressed activity of GSK-3β. The addition of LY294002, a PI3K inhibitor, could suppress phosphorylation of Akt and CREB and activate GSK-3β, resulting in abolishment of neuroprotective effects of rifampicin on cells exposed to rotenone. Rifampicin provides neuroprotection against dopaminergic degeneration, partially via the PI3K/Akt/GSK-3β/CREB signaling pathway. These findings suggest that rifampicin could be an effective and promising neuroprotective candidate for treating PD.

Novel biomolecular information in rotenone-induced cellular model of Parkinson's disease

In order to uncover the remarkable pathogenic genes or molecular pathological process in Parkinsons disease (PD), we employed a microarray analysis upon the cellular PD model induced by rotenone. Compared to the control group, 2174 genes were screened out to be expressed differently in the rotenone-induced group by certain criterion. GO analysis and the pathways analysis showed the significant enrichment of genes that were associated with the biological process of cell cycle, apoptotic process, organelle fusion, mitochondrial lesion, endoplasmic reticulum stress and so on. Among these significant DE genes, some were sorted out to be involved in cell cycle and protein processing in endoplasmic reticulum. As the PPI network analysis showed, the interaction relationship of the DEGs involved in the process of protein generation in endoplasmic reticulum(ER) was clearly showed up. As a prediction, we emphasized the genes EDEM1, ATF4, TRAF2 might play central roles in the protein misfolding process during the progression of Parkinsons disease and these new-found genes might be the future research focus and therapeutic targets in PD.