Hypoxic preconditioning induced neuroprotection against cerebral ischemic injuries and its cPKCγ-mediated molecular mechanism

Zhang, Nan; Yin, Yanling; Han, Song; Jiang, Jun; Yang, Weiwei; Bu, Xiangning; Li, Junfa

doi:10.1016/j.neuint.2011.02.007

Cited by 50 publications

(45 citation statements)

References 48 publications

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“…1–6 RIC has potential clinical applications in the prevention of cerebral ischemia, as it can be applied without exposing the brain to unnecessary risk. The mechanism of ischemic protection underlying RIC is likely multifactorial and includes down-regulation of genes associated with inflammation, 7,8 reduction of glutamatergic excitotoxicity, 9,10 blockage of apoptotic neuronal pathways, 11,12 and increase in blood flow to the ischemic penumbra. 13 …”

Section: Introductionmentioning

confidence: 99%

Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage

et al. 2014

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Background Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit (DIND) after aneurysmal subarachnoid hemorrhage (aSAH). While RIC has been extensively investigated in animal models, it has not been fully evaluated in humans. Objective To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial. Methods Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to four RIC sessions on non-consecutive days. Primary endpoints were (1) the development of a symptomatic deep venous thrombosis (DVT), bruising or injury to the limb and, (2) request to stop by the patient or surrogate. The secondary endpoints were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up. Results Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a DVT or injury to the preconditioned limb. No Patient developed DIND during their enrollment. At follow-up, median modified Rankin Scale was 1 and Glasgow Outcome Score was 5. Conclusion The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.

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Section: Introductionmentioning

confidence: 99%

Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage

et al. 2014

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“…The Infarct size coefficient of variation (in the total 500 control groups9101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109110…”

Section: Resultsmentioning

confidence: 99%

Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis

Ingberg

Dock

Theodorsson

et al. 2016

Sci Rep

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Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters’ impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

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“…Previous studies have identified that within hypertrophic cells of a brain that has suffered a stroke, overexpression of SPNA2 and DPYSL2 (also known as CRMP2 ) was revealed to be correlated with neurite outgrowth and plasticity, which suggests an early activation of neuronal regeneration, repair and development (36,37). Meanwhile, in the neonatal rat brain, the Akt/glycogen synthase kinase-3β/ CRMP2 pathway modulates axonal injury following hypoxia-ischemia (38,39). Thus, the expression levels of CRMP1 and DPYSL2 may be associated with the effect of inflammation on neurotransmission of VSMC.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes associated with the effect of inflammation on the neurotransmission of vascular smooth muscle cell

Gan

Qiu

Feng

et al. 2017

Experimental and Therapeutic Medicine

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Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in vascular disorders, and inflammation has a crucial role in the development of these diseases. To investigate the effect of inflammation on the neurotransmission of VSMC, bioinformatic analysis was performed, following next generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next generation sequencing, and each assay was repeated three times. Differentially expressed genes (DEGs) were obtained using the NOISeq package in R. Subsequently, their potential functions were predicted by functional and pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery online tool. Interaction relationships of the proteins enriched in pathways associated with neurological diseases, the proteins which had interaction relationships with adrenoceptor α 1D (ADRA1D) or calcium voltage-gated channel subunit α1 S (CACNA1S), separately, were obtained from STRING, and protein-protein interaction (PPI) networks were constructed using Cytoscape software. A total of 2,038 DEGs, including 1,094 upregulated and 944 downregulated genes in the LPS treatment group were identified when compared with the control group. Enrichment analyses showed that NADH:Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2) was involved in several neurological diseases, including oxidative phosphorylation, Alzheimer's disease, Parkinson's disease and Huntington's disease. Furthermore, NDUFV2 (degree, 20) had a higher degree in the PPI network for DEGs enriched in pathways associated with neurological diseases. In the PPI network for ADRA1D, CACNA1S and the DEGs interacting with them, prohibitin (PHB), oxytocin receptor (OXTR), collapsin response mediator protein 1 (CRMP1) and dihydropyrimidinase like 2 (DPYSL2) had interaction relationships with both ADRA1D and CACNA1S. To conclude, the present study revealed that NDUFV2, PHB, OXTR, CRMP1 and DPYSL2 may have key roles in the effect of inflammation on neurotransmission of VSMC.

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Hypoxic preconditioning induced neuroprotection against cerebral ischemic injuries and its cPKCγ-mediated molecular mechanism

Cited by 50 publications

References 48 publications

Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage

Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage

Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis

Identification of genes associated with the effect of inflammation on the neurotransmission of vascular smooth muscle cell

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