scholarly journals Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Juan Liu ◽  
Kun-shan Zhang ◽  
Bin Hu ◽  
Si-guang Li ◽  
Qing Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Expression Profiles ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Rna Regulation ◽  
Systematic Analysis ◽  
Short Interspersed Elements ◽  
Regulation Network ◽  
Cerebral Artery Occlusion

Although extensive studies have identified large number of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE) mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD) which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA) hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

scholarly journals Treatment Effects of Ischemic Stroke by Berberine, Baicalin, and Jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) Explored by an Integrated Metabolomics Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-20 ◽  
Author(s):  
Qian Zhang ◽  
Xiaowei Fu ◽  
Junsong Wang ◽  
Minghua Yang ◽  
Lingyi Kong
Keyword(s):  
Ischemic Stroke ◽  
Treatment Effects ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
H Nmr ◽  
Abnormal Metabolism ◽  
Cerebral Artery Occlusion ◽  
First Time ◽  
Integrated Metabolomics

Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the 1H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects.

scholarly journals CD28 Superagonist-Mediated Boost of Regulatory T Cells Increases Thrombo-Inflammation and Ischemic Neurodegeneration during the Acute Phase of Experimental Stroke

2014 ◽  
Vol 35 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Michael K Schuhmann ◽  
Peter Kraft ◽  
Guido Stoll ◽  
Kristina Lorenz ◽  
Sven G Meuth ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Thrombus Formation ◽  
Inflammatory Lesion ◽  
Artery Occlusion ◽  
Acute Stage ◽  
Experimental Stroke ◽  
Cerebral Artery Occlusion

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

scholarly journals Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Kathleen E. Salmeron ◽  
Michael E. Maniskas ◽  
Danielle N. Edwards ◽  
Raymond Wong ◽  
Ivana Rajkovic ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Side Effects ◽  
Carotid Artery ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Interleukin 1 ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

Abstract Background Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016). Methods Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses. Results We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair. Conclusions Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.

scholarly journals Deletion of ubiquitin ligase Nedd4l exacerbates ischemic brain damage

2020 ◽  
pp. 0271678X2094380
Author(s):  
TaeHee Kim ◽  
Anil K Chokkalla ◽  
Raghu Vemuganti
Keyword(s):  
Brain Damage ◽  
Cortical Neurons ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Motor Dysfunction ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
E3 Ligases ◽  
Cerebral Artery Occlusion

Ubiquitination by Nedd4 (neuronally expressed developmentally downregulated 4) family of HECT type E3 ligases plays a key role in degrading misfolded and damaged proteins, and its disruption leads to neurodegeneration. Parkinson's disease-causing protein α-Synuclein (α-Syn) is ubiquitinated by the Nedd4 family and degraded by endosomes. Nedd4l is the only Nedd4 homolog that showed upregulation in post-stroke surviving cortical neurons where it correlated with neuroprotection. We tested the role of Nedd4l after stroke by subjecting the Nedd4l−/− mice to transient middle cerebral artery occlusion. Focal ischemia significantly increased Nedd4l expression and poly-ubiquitinated α-Syn levels, and knockout of Nedd4l reduced post-ischemic poly-ubiquitinated α-Syn that is majorly located in the peri-infarct neurons. Co-immunoprecipitation further shows that focal ischemia enhances the α-Syn-Nedd4l interaction resulting in increased ubiquitination of α-Syn. Nedd4l knockout mice ( n = 7 mice/group) showed exacerbated post-ischemic motor dysfunction manifested by decreased time on the rotarod and increased number of foot faults, and significantly increased ischemic brain damage. This suggests that Nedd4l might be a potential therapeutic target to minimize α-Syn-mediated toxicity after cerebral ischemia.

scholarly journals Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation

2020 ◽  
Vol 21 (18) ◽  
pp. 6954
Author(s):  
Li-Ming Lien ◽  
Wan-Jung Lu ◽  
Ting-Yu Chen ◽  
Tzu-Yin Lee ◽  
Hsueh-Hsiao Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombus Formation ◽  
Artery Occlusion ◽  
Pulmonary Thrombosis ◽  
Neurological Severity Score ◽  
Phospholipase D1 ◽  
Redundant Functions ◽  
Cerebral Artery Occlusion ◽  
Increase Survival Rate

Previously, we reported that phospholipase D1 (PLD1) and PLD2 inhibition by selective PLD1 and PLD2 inhibitors could prevent platelet aggregation in humans, but not in mice. Moreover, only the PLD1 inhibitor, but not PLD2 inhibitor, could effectively prevent thrombus formation in mice, indicating that PLD might play different roles in platelet function in humans and mice. Although PLD1 and PLD2 were reported to be implicated in thrombotic events, the role of PLD in mice remains not completely clear. Here, we investigated the role of PLD1 and PLD2 in acute pulmonary thrombosis and transient middle cerebral artery occlusion-induced brain injury in mice. The data revealed that inhibition of PLD1, but not of PLD2, could partially prevent pulmonary thrombosis-induced death. Moreover, concurrent PLD1 and PLD2 inhibition could considerably increase survival rate. Likewise, inhibition of PLD1, but not PLD2, partially improved ischemic stroke and concurrent inhibition of PLD1, and PLD2 exhibited a relatively better protection against ischemic stroke, as evidenced by the infarct size, brain edema, modified neurological severity score, rotarod test, and the open field test. In conclusion, PLD1 might play a more important role than PLD2, and both PLD1 and PLD2 could act synergistically or have partially redundant functions in regulating thrombosis-relevant events.

Abstract 176: Platelet Cyclophilin D Mediates Neutrophil Recruitment and Ischemic Stroke Outcomes in Mice

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Frederik Denorme ◽  
Bhanukanth Manne ◽  
Yasuhiro Kosaka ◽  
Jennifer Majersik ◽  
Benjamin Kile ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Infarct Volume ◽  
Human Platelets ◽  
Artery Occlusion ◽  
Cyclophilin D ◽  
Stroke Outcomes ◽  
Fold Reduction ◽  
Cerebral Artery Occlusion

Rationale: Besides their role in thrombosis, platelets also mediate inflammation through platelet-neutrophil aggregates (PNA). Recently, cyclophilin D (CypD)-mediated platelet necrosis emerged as a potential mediator of detrimental PNA during thrombosis. However, the role of platelet CypD in ischemic stroke has never been examined. Objective: Here, we investigate the contribution of platelet CypD following ischemic stroke. Methods: We generated mice lacking CypD specifically in platelets (KO). Both wild-type (WT) and KO mice were subjected to a 1h transient middle cerebral artery occlusion (tMCAO) stroke model. Twenty-four hours after occlusion, neurological and motor function, and stroke infarct size were determined. We also examined if the CypD pathway was altered in human platelets after ischemic stroke. Results: Loss of platelet CypD significantly improved neurological (p<0.001) and motor (p<0.005) functions compared to WT mice after tMCAO. Furthermore, platelet CypD deficient significantly reduced ischemic stroke infarct volume (39.1±15.7mm 3 vs. 78.6±27.7mm 3 , n=15; p<0.0001). Smaller infarcts in KO mice was not due to difference in blood flow during the ischemia stage. Twenty-four hours after stroke, a greater than 2-fold reduction in neutrophils was observed in the brains from KO mice (p<0.0001). In addition, we observed significantly fewer circulating and cerebral PNA (p<0.01). Depletion of neutrophils significantly (p<0.05) reduced infarct size and neurological damage following ischemic stroke in WT mice, however, no additional protective effect was observed in KO mice, suggesting necrotic PNAs are critical during ischemic stroke. RNA-sequencing on platelets isolated from ischemic stroke patients (n=8) and healthy aged, gender matched controls (n=7) revealed significant increases in several targets involved in CypD-mediated necrosis, including MCUR1, TMEM16F and calpain2 (p<0.005). Conclusion: Our results demonstrate necrotic platelets interact with neutrophils to exacerbate brain injury following ischemic stroke. As inhibiting platelet necrosis does not compromise hemostasis, targeting platelet CypD may be a potential therapeutic strategy to limit brain damage after ischemic stroke.

MICROGLYOCYTES MORPHOLOGY AFTER FOCAL ISCHEMIC STROKE IN A MOUSE BRAIN

2020 ◽  
Author(s):  
Анастасия Александровна Гиганова ◽  
Татьяна Викторовна Ананьина ◽  
Алёна Андреевна Кисель ◽  
Марина Юрьевна Ходанович
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Mouse Brain ◽  
Gray Matter ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Cytological Analysis ◽  
Cerebral Artery Occlusion ◽  
Microglia Morphology

Проведен цитологический анализ изменения морфологии микроглиоцитов в мозге мышей, перенесших локальную ишемию головного мозга посредством окклюзии средней мозговой артерии (MCAO). Описана специфика изменения морфологии микроглиоцитов в белом и сером веществе головного мозга в ипсилатеральном полушарии. It was performed the cytological analysis of microglia morphology in mice underwent focal ischemia by means of middle cerebral artery occlusion (MCAO). The features of morphological microglyocyte changes in a white and gray matter of ipsilateral lesioned hemisphere was described.

scholarly journals Role of Neuroimaging in Guiding Treatment Decisions on Endovascular Thrombectomy

2017 ◽  
Vol 01 (01) ◽  
pp. E18-E27
Author(s):  
Daniel Kaiser ◽  
Johannes Gerber ◽  
Volker Puetz
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Vascular Occlusion ◽  
Artery Occlusion ◽  
Infarct Core ◽  
Endovascular Thrombectomy ◽  
Non Invasive ◽  
Cerebral Artery Occlusion

AbstractSix recent randomized controlled trials showed a significant benefit of endovascular therapy on patient outcome in acute ischemic stroke due to anterior cerebral artery occlusion. The positive results of these trials need to be implemented in clinical routine. Suitable patients should be evaluated for thrombectomy reliably and fast. All trials confirmed the role of pretherapeutic neuroimaging as crucial in selecting patients who can benefit from endovascular therapy. However, different approaches have been used, including imaging of the target vascular occlusion, infarct core, arterial collateral supply or the penumbra. In this review we discuss, in the context of the recent trials, the different methods of non-invasive neuroimaging and their role in decision-making for thrombectomy in acute ischemic stroke.

Energy-Sensing Pathways in Ischemia: The Counterbalance Between AMPK and mTORC

2020 ◽  
Vol 25 (45) ◽  
pp. 4763-4770
Author(s):  
Angel Cespedes ◽  
Mario Villa ◽  
Irene Benito-Cuesta ◽  
Maria J. Perez-Alvarez ◽  
Lara Ordoñez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cause Of Death ◽  
Artery Occlusion ◽  
Brain Pathology ◽  
Common Cause ◽  
Specific Analysis ◽  
Energy Sensing ◽  
Cerebral Artery Occlusion

: Stroke is an important cause of death and disability, and it is the second leading cause of death worldwide. In humans, middle cerebral artery occlusion (MCAO) is the most common cause of ischemic stroke. The damage occurs due to the lack of nutrients and oxygen contributed by the blood flow. : The present review aims to analyze to what extent the lack of each of the elements of the system leads to damage and which mechanisms are unaffected by this deficiency. We believe that the specific analysis of the effect of lack of each component could lead to the emergence of new therapeutic targets for this important brain pathology.

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