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Source: Molecular Neurobiology
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Total 278 results found since Jan 2013.
Toll-Like Receptor 4 Signaling in Focal Cerebral Ischemia: a Focus on the Neurovascular Unit
AbstractA robust innate immune activation leads to downstream expression of inflammatory mediators that amplify tissue damage and consequently increase the morbidity after stroke. The Toll-like receptor 4 (TLR4) pathway is a major innate immune pathway activated acutely and chronically after stroke. Hence, understanding the intricacies of the temporal profile, specific control points, and cellular specificity of TLR4 activation is crucial for the development of any novel therapeutics targeting the endogenous innate immune response after focal cerebral ischemia. The goal of this review is to summarize the current findings r...
Source: Molecular Neurobiology - April 17, 2020 Category: Neurology Source Type: research
cGAS/STING Pathway Activation Contributes to Delayed Neurodegeneration in Neonatal Hypoxia-Ischemia Rat Model: Possible Involvement of LINE-1
AbstractcGAS is a sensor of cytosolic DNA and responds equally to exogenous and endogenous DNA. After recognition of cytosolic dsDNA or ssDNA, cGAS synthesizes the second messenger 2 ′3′-cGAMP, which then binds to and activates stimulator of interferon genes (STING). STING plays an essential role in responding to pathogenic DNA and self-DNA in the context of autoimmunity. In pathologic conditions, such as stroke or hypoxia-ischemia (HI), DNA can gain access into the cytoplas m of the cell and leak from the dying cells into the extracellular environment, which potentially activates cGAS/STING. Recent in vivo studies of ...
Source: Molecular Neurobiology - April 5, 2020 Category: Neurology Source Type: research
NLRP3 Depletion Fails to Mitigate Inflammation but Restores Diminished Phagocytosis in BV-2 Cells After In Vitro Hypoxia
AbstractPost-hypoxic/ischemic neuroinflammation is selectively driven by sterile inflammation, which implies the interplay of brain-intrinsic immune cells with other neural cells and immigrated peripheral immune cells. The resultant inflammatory cascade evolves extra- and intracellular pathogen and danger-associated receptors. The latter interacts with multiprotein complexes termed inflammasomes. The NLRP3 inflammasome is one of the best-described inflammasomes. However, its impact on post-ischemic neuroinflammation and its role in neuroprotection after ischemic stroke are still under debate. Microglial cells are known to ...
Source: Molecular Neurobiology - March 31, 2020 Category: Neurology Source Type: research
Tissue Plasminogen Activator Promotes TXNIP-NLRP3 Inflammasome Activation after Hyperglycemic Stroke in Mice
AbstractHyperglycemia has been shown to counterbalance the beneficial effects of tissue plasminogen activator (tPA) and increase the risk of intracerebral hemorrhage in ischemic stroke. Thioredoxin interacting protein (TXNIP) mediates hyperglycemia-induced oxidative damage and inflammation in the brain and reduces cerebral glucose uptake/utilization. We have recently reported that TXNIP-induced NLRP3 (NOD-like receptor pyrin domain-containing-3) inflammasome activation contributes to neuronal damage after ischemic stroke. Here, we tested the hypothesis that tPA induces TXNIP-NLRP3 inflammasome activation after ischemic str...
Source: Molecular Neurobiology - March 13, 2020 Category: Neurology Source Type: research
Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina
AbstractThe retina is an extension of the central nervous system and has been considered to be a simplified, more tractable and accessible version of the brain for a variety of neuroscience investigations. The optic nerve displays changes in response to underlying neurodegenerative diseases, such as stroke, multiple sclerosis, and Alzheimer ’s disease, as well as inner retinal neurodegenerative disease, e.g., glaucoma. Neurodegeneration has increasingly been linked to dysfunctional energy metabolism or conditions in which the energy supply does not meet the demand. Likewise, increasing lactate levels have been correlated...
Source: Molecular Neurobiology - January 7, 2020 Category: Neurology Source Type: research
Sphingosine 1-Phosphate Signaling Is Involved in Impaired Blood –Brain Barrier Function in Ischemia–Reperfusion Injury
AbstractSphingosine 1-phosphate (S1P) is a major bioactive lipid mediator in the vascular and immune system. Here, we have shown that inhibition of S1P signaling prevents blood –brain barrier (BBB) dysfunction after ischemia both in vitro and in vivo. In the in vitro BBB models, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of an S1P synthesizing enzyme (Sphk1) and S1P transporters (Abca1, Spns2), increasing S1P in culture media. Inhibitors of Sphk1 (SKI-II) or Abca1 (probucol) attenuated the decrease in transendothelial electrical resistance and the increase in permeability caused by OGD/R...
Source: Molecular Neurobiology - December 3, 2019 Category: Neurology Source Type: research
Transcriptional Response and Morphological Features of the Neurovascular Unit and Associated Extracellular Matrix After Experimental Stroke in Mice
In conclusion, the variety in gene regulation emphasizes the complexity of interactions within the ischemia-affected NVU and ECM. These data might help to focus future res earch on a set of highly sensitive elements, which might prospectively facilitate neuroprotective strategies beyond the traditional single target perspective.
Source: Molecular Neurobiology - October 26, 2019 Category: Neurology Source Type: research
Glia-Like Cells from Late-Passage Human MSCs Protect Against Ischemic Stroke Through IGFBP-4
AbstractStem cell therapy is considered to be a promising future treatment for intractable neurological diseases, although all the clinical trials using stem cells have not yet shown any good results. Early passage mesenchymal stem cells (MSCs) have been used in most clinical trials because of the issues on safety and efficacy. However, it is not easy to get plenty of cells enough for the treatment and it costs too much. Lots of late passage MSCs can be obtained at lower cost but their efficacy would be a big hurdle for clinical trials. If late passage MSCs with better efficacy could be used in clinical trials, it could be...
Source: Molecular Neurobiology - October 26, 2019 Category: Neurology Source Type: research
Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation
AbstractMitochondrial dysfunction and oxidative stress play a key role in ischemia/reperfusion (I/R) induced brain injury. We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. We demonstrate here that nialamide (NM), a non-selective monoamine oxidase (MAO) inhibitor, upregulated Ublqn1 and protected neurons from oxygen-glucose deprivation- and I/R-caused cell death in in vitro and in vivo, respectively. Post-ischemic administration of the NM in a stroke mouse model even at 3 h following I/R still reduced ...
Source: Molecular Neurobiology - October 14, 2019 Category: Neurology Source Type: research
Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
AbstractFood composition influences stroke risk, but its effects on ischemic injury and neurological deficits are poorly examined. While severe reduction of protein content was found to aggravate neurological impairment and brain injury as a consequence of combined energy-protein malnutrition, moderate protein restriction not resulting in energy deprivation was recently suggested to protect against perinatal hypoxia-ischemia. Male C57BL6/j mice were exposed to moderate protein restriction by providing a normocaloric diet containing 8% protein (control: 20% protein) for 7, 14, or 30 days. Intraluminal middle cerebral arte...
Source: Molecular Neurobiology - June 30, 2019 Category: Neurology Source Type: research
Contribution of Serum Lipid Profiles to Outcome After Endovascular Thrombectomy for Anterior Circulation Ischemic Stroke
AbstractThe contribution of lipids, including low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and triglycerides (TG), to stroke outcomes is still debated. We sought to determine the impact of LDL-C concentrations on the outcome of patients with ischemic stroke in the anterior circulation who received treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of consecutive patients with acute ischemic stroke treated at a tertiary center between 2012 and 2016. Patients treated with EVT for large artery occlusion in the anterior circulation were selected. The primary e...
Source: Molecular Neurobiology - May 7, 2019 Category: Neurology Source Type: research
Alteration of microRNA 340-5p and Arginase-1 Expression in Peripheral Blood Cells during Acute Ischemic Stroke
AbstractAcute stroke alters the systemic immune response as can be observed in peripheral blood; however, the molecular mechanism by which microRNA (miRNA) regulates target gene expression in response to acute stroke is unknown. We performed a miRNA microarray on the peripheral blood of 10 patients with acute ischemic stroke and 11 control subjects. Selected miRNAs were quantified using a TaqMan assay. After searching for putative targets from the selected miRNAs using bioinformatic analysis, functional studies including binding capacity and protein expression of the targets of the selected miRNAs were performed. The resul...
Source: Molecular Neurobiology - April 23, 2019 Category: Neurology Source Type: research
Novel miRNA PC-5P-12969 in Ischemic Stroke
AbstractCirculating microRNAs (miRNAs) have been used effectively as peripheral biomarkers and mechanistic targets for human diseases such as stroke, Alzheimer ’s, and cancer. The purpose of our study is to determine noninvasive, blood-based early detectable biomarkers for ischemic stroke (IS). Based on our previous global miRNA sequencing study, four miRNAs were previously unreported (novel) in IS condition. Among these, miRNA PC-5P-12969 was exclusivel y expressed in the IS condition; otherwise, it was not expressed in normal condition, and therefore, we focused on miRNA PC-5P-12969 for further studies. In the present ...
Source: Molecular Neurobiology - April 4, 2019 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
Inhibition of Toll-Like Receptor-4 (TLR-4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats: Possible Role of Vascular Endothelial TLR-4
In conclusion, TLR-4 is highly upregulated in the microvasculature and that beneficial effects of TLR-4 inhibition are more profound in diabetes. This suggests that inhibition of vascular TLR-4 may provide therapeutic benefits for stroke recovery in diabetes.
Source: Molecular Neurobiology - February 27, 2019 Category: Neurology Source Type: research
