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G-Protein-Coupled Receptors and Ischemic Stroke: a Focus on Molecular Function and Therapeutic Potential
AbstractIn ischemic stroke, there is only one approved drug, tissue plasminogen activator, to be used in clinical conditions for thrombolysis. New neuroprotective therapies for ischemic stroke are desperately needed. Several targets and pathways have been shown to confer neuroprotective effects in ischemic stroke. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system disorders. GPCRs are a large family of cell surface receptors that response to a wide variety of extracellular stimuli. GPCRs are involved in a wide range of physiolog...
Source: Molecular Neurobiology - June 12, 2021 Category: Neurology Source Type: research

ADAMTS9-AS2 Promotes Angiogenesis of Brain Microvascular Endothelial Cells Through Regulating miR-185-5p/IGFBP-2 Axis in Ischemic Stroke
AbstractIschemic stroke is a common disease threatening human health. ADAMTS9-AS2 is a lncRNA that has been widely studied in tumors, but not in ischemic stroke. The purpose of this study was to investigate the role and potential molecular mechanism of ADAMTS9-AS2 in endothelial cell function after ischemic stroke in vivo and in vitro. The results showed that ADAMTS9-AS2 was decreased in the plasma of acute ischemic stroke (AIS) patients and in the brain tissue and plasma of MCAO mice, and the low expression of ADAMTS9-AS2 was associated with the increase in infarct size. Besides, compared with the control group, MCAO trea...
Source: Molecular Neurobiology - January 31, 2022 Category: Neurology Source Type: research

Neuroprotective Effect of E3 Ubiquitin Ligase RNF8 Against Ischemic Stroke via HDAC2 Stability Reduction and Reelin-Dependent GSK3 β Inhibition
AbstractLoss of E3 ubiquitin ligase RING finger protein 8 (RNF8) may lead to neuronal DNA damage and apoptosis. In order to expand on our knowledge on the mechanistic basis underlying neuronal death in ischemic stroke, the present study sought to investigate the potential role of E3 ubiquitin ligase RNF8 on ischemic stroke and explore the underlying downstream mechanism. Middle cerebral artery occlusion (MCAO) in mice and oxygen –glucose deprivation/reoxygenation (OGD/R) in neurons were induced to simulate an ischemic stroke environment. It was found that downregulation of RNF8 and Reelin occurred in MCAO mice and OGD/R-...
Source: Molecular Neurobiology - May 27, 2022 Category: Neurology Source Type: research

Elevated Serum Mannose-Binding Lectin Levels Are Associated with Poor Outcome After Acute Ischemic Stroke in Patients with Type 2 Diabetes
Abstract The activation of the complement system may be involved in the pathology of stroke and type 2 diabetes (T2DM). We therefore evaluated the long-term prognostic value of early measurement of serum mannose-binding lectin (MBL) levels, an activator of the complement system, in Chinese T2DM with acute ischemic stroke (AIS). Serum MBL levels were determined in T2DM patients with AIS (N = 188). The adjudicated end points were 1-year functional outcomes and mortality. The prognostic value of MBL was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Pat...
Source: Molecular Neurobiology - October 25, 2014 Category: Neurology Source Type: research

Association Between Matrix Metalloproteinase Family Gene Polymorphisms and Ischemic Stroke: a Meta-analysis
The objective of this study was to evaluate the relationships between MMP gene polymorphisms and ischemic stroke by using a meta-analysis. The PubMed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated. Eleven studies were enrolled, including a total of 589 cases and 494 controls of MMP-1 -1607 1G/2G; 1,817 cases and 1,731 controls of MMP-3 -1612 5A/6A; and 540 cases and 547 controls of MMP-9 -1562C/T. Under the dominant and recessive models, respectively, the overall ORs and 95 ...
Source: Molecular Neurobiology - November 10, 2014 Category: Neurology Source Type: research

Thioredoxin-Interacting Protein: a Novel Target for Neuroprotection in Experimental Thromboembolic Stroke in Mice
This study also affirms the importance of the antioxidant effect of RES on the TRX/TXNIP system.
Source: Molecular Neurobiology - March 14, 2015 Category: Neurology Source Type: research

Nrf2 Weaves an Elaborate Network of Neuroprotection Against Stroke
Abstract Nuclear factor erythroid 2-related factor 2 (Nrf2) is a neuroprotective transcription factor that has recently attracted increased attention. Stroke, a common and serious neurological disease, is currently a leading cause of death in the USA so far. It is therefore of vital importance to explore how Nrf2 behaves in stroke. In this review, we first introduce the structural features of Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) and briefly depict the activation, inactivation, and regulation processes of the Nrf2 pathway. Next, we discuss the physiopathological mechanisms, upstream modulators, and ...
Source: Molecular Neurobiology - February 5, 2016 Category: Neurology Source Type: research

Endovascular Treatment Versus Intravenous Thrombolysis for Acute Ischemic Stroke: a Quantitative Review and Meta-Analysis of 21 Randomized Trials
Abstract Emerging studies suggest that endovascular treatment (EVT) may be superior to intravenous thrombolysis for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) to assess the efficacy and safety of endovascular treatment in patients with acute ischemic stroke as compared with intravenous thrombolysis. We assessed RCTs investigating EVT versus intravenous thrombolysis (IVT) published up to June 2015. In total, 21 studies of 4473 patients were included in the systematic review and meta-analysis. EVT significantly improved functional outcom...
Source: Molecular Neurobiology - February 3, 2016 Category: Neurology Source Type: research

N-Myc Downstream-Regulated Gene 2 (Ndrg2) Is Involved in Ischemia–Hypoxia-Induced Astrocyte Apoptosis: a Novel Target for Stroke Therapy
In conclusion, NDRG2 is involved in astrocyte apoptosis following ischemic–hypoxic injury, and inhibiting NDRG2 expression significantly reduces ROS production and astrocyte apoptosis. These findings provide insight into the role of NDRG2 in ischemic–hypoxic injury and provide potential targets for future clinical therapies for stroke.
Source: Molecular Neurobiology - May 5, 2016 Category: Neurology Source Type: research

Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke
This study investigated shortened dosage schedules of DDFPe in nonstandard posterior (NSTND) strokes following occlusions of the posterior cerebral arteries. DDFPe given at shortened schedules of 30 or 60-min injection intervals will reduce neurological deficits, percent stroke volume (%SV), and serum glutamate levels in NSTND ischemic strokes. New Zealand White rabbits (N = 26) were randomly placed into three groups: A (n = 9) controls given saline injections every 60 min, B (n = 9) 2 % DDFPe given IV every 30 min, and C (n = 8) DDFPe every 60 min. Injections began 1 h after embolization. Groups were subdivid...
Source: Molecular Neurobiology - July 13, 2017 Category: Neurology Source Type: research

Canonical Wnt Pathway Maintains Blood-Brain Barrier Integrity upon Ischemic Stroke and Its Activation Ameliorates Tissue Plasminogen Activator Therapy
AbstractStroke induces blood-brain barrier (BBB) breakdown, which promotes complications like oedema and hemorrhagic transformation. Administration of recombinant tissue plasminogen activator (rtPA) within a therapeutic time window of 4.5  h after stroke onset constitutes the only existing treatment. Beyond this time window, rtPA worsens BBB breakdown. Canonical Wnt pathway induces BBB formation and maturation during ontogeny. We hypothesized that the pathway is required to maintain BBB functions after stroke; thus, its activation m ight improve rtPA therapy. Therefore, we first assessed pathway activity in the brain of m...
Source: Molecular Neurobiology - March 8, 2019 Category: Neurology Source Type: research

Cross-Talk Between Key Players in Patients with COVID-19 and Ischemic Stroke: A  Review on Neurobiological Insight of the Pandemic
AbstractThe global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore ...
Source: Molecular Neurobiology - October 7, 2020 Category: Neurology Source Type: research

Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke
AbstractStroke is one of the main causes of neurological disability worldwide and the second cause of death in people over 65  years old, resulting in great economic and social burden. Ischemic stroke accounts for 85% of total cases, and the approved therapies are based on re-establishment of blood flow, and do not directly target brain parenchyma. Thus, novel therapies are urgently needed. In this review, limb remote isc hemic conditioning (RIC) is revised and discussed as a potential therapy against ischemic stroke. The review targets both (i) fundamental research based on experimental models and (ii) clinical research ...
Source: Molecular Neurobiology - October 22, 2021 Category: Neurology Source Type: research

SATB1/SLC7A11/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection
AbstractNeuronal damage after ischemic stroke (IS) is frequently due to ferroptosis, contributing significantly to ischemic injury. However, the mechanism against ferroptosis in IS remained unclear. The aim of this study was to investigate the potential mechanism of Danhong injection (DHI) and the critical transcription factor SATB1 in preventing neuronal ferroptosis after ischemic stroke in vivo and in vitro. The results showed that DHI treatment significantly reduced the infarct area and associated damage in the brains of the pMCAO mice, and enhanced the viability of OGD-injured neurons. And several characteristic indica...
Source: Molecular Neurobiology - December 17, 2022 Category: Neurology Source Type: research

Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke
In this study, overexpression of CREB protein in pyramidal neurons in vCA1 by AAV virus significantly upregulated the content of BDNF and ameliorated the dysfunction induced by ischemic stroke. Our results demonstrated activation of the CREB-BDNF pathway in vCA1 pyramidal neurons significantly improved neurological deficits, pain perception, anxiety, and depression induced by ischemic stroke.
Source: Molecular Neurobiology - March 3, 2023 Category: Neurology Source Type: research

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