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Source: Molecular Neurobiology
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Total 278 results found since Jan 2013.
Delayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective
AbstractGalectin-3 (Gal-3), a β-galactoside-binding lectin, has recently emerged as a molecule with immunoregulatory functions. We investigated the effects of Gal-3 on microglia morphology, migration, and secretory profile under physiological conditions and in the context of ischemic injury. We show that in the control conditio ns, exposure to recombinant Gal-3 increases microglial ramification and motility in vitro and in vivo via an IL-4-dependent mechanism. Importantly, after stroke, Gal-3 exerted marked immune-modulatory properties. Delivery of Gal-3 at 24 h after middle cerebral artery occlusion (MCAO) was associate...
Source: Molecular Neurobiology - February 23, 2019 Category: Neurology Source Type: research
Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death
AbstractNR4A2 is a nuclear receptor and a transcription factor, with distinctive physiological features. In the cell nuclei of the central nervous system, it is widely expressed and identified as a crucial regulator of dopaminergic (DA) neuronal differentiation, survival, and maintenance. Importantly, it has regulated different genes crucial for dopaminergic signals, and its expression has been diminished in both aged and PD post-mortem brains and reduced in PD patients. In microglia and astrocytes, the expression of NR4A2 has been found where it can be capable of inhibiting the expression of proinflammatory mediators; hen...
Source: Molecular Neurobiology - January 25, 2019 Category: Neurology Source Type: research
Bilirubin and Ischemic Stroke: Rendering the Current Paradigm to Better Understand the Protective Effects of Bilirubin
AbstractNovel and innovative methods are critical in fostering new treatments and improving clinical outcomes in patients who suffer from ischemic stroke. Bilirubin has long been considered metabolic waste that can be harmful to the body; however, it is now becoming recognized as one of the body ’s most potent antioxidant, anti-inflammatory, and neuroprotective molecules. These properties facilitate bilirubin’s anti-atherogenic effects to impede and prevent the formation of thrombi in ischemic stroke. These functions allow for protection from neuronal injury during an ischemic state and suggest that elevated bilirubin ...
Source: Molecular Neurobiology - January 5, 2019 Category: Neurology Source Type: research
miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells
AbstractEndothelial dysfunction is a key element in cerebral small vessel disease (CSVD), which may cause stroke and cognitive decline. Cyclic nucleotide signaling modulates endothelial function. The cyclic adenosine monophosphate-degrading enzyme phosphodiesterase 3 (PDE3) is an important treatment target which may be modulated by microRNAs (miRNAs) important for regulating gene expression. We aimed to identify PDE3-targeting miRNAs to highlight potential therapeutic targets for endothelial dysfunction and CSVD. PDE3-targeting miRNAs were identified by in silico analysis (TargetScan, miRWalk, miRanda, and RNA22). The iden...
Source: Molecular Neurobiology - January 2, 2019 Category: Neurology Source Type: research
Improved Reperfusion and Vasculoprotection by the Poly(ADP-Ribose)Polymerase Inhibitor PJ34 After Stroke and Thrombolysis in Mice
In conclusion, the combination of the PARP inhibitor PJ34 with rt-PA after cerebral ischemia may be of particular interest in order to improve thrombolysis with an extended therapeutic window.
Source: Molecular Neurobiology - October 26, 2018 Category: Neurology Source Type: research
Exosomes in Acquired Neurological Disorders: New Insights into Pathophysiology and Treatment
AbstractExosomes are endogenous nanovesicles that play critical roles in intercellular signaling by conveying functional genetic information and proteins between cells. Exosomes readily cross the blood-brain barrier and have promise as therapeutic delivery vehicles that have the potential to specifically deliver molecules to the central nervous system (CNS). This unique feature also makes exosomes attractive as biomarkers in diagnostics, prognostics, and therapeutics in the context of multiple significant public health conditions, including acquired neurological disorders. The purpose of this review is to summarize the sta...
Source: Molecular Neurobiology - October 26, 2018 Category: Neurology Source Type: research
Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis
In this study, we used fluid percussion injury in rats to simulate mild TBI. For rats, we used both passive avoidance learning and the Y-maze tests to evaluate cognitive function. We investigated whether PE rehabilitation attenuated cognitive deficits in rats with TBI and determined the contribution of hippocampal and cortical expression of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery. In addition to increasing hippocampal and cortical expression of HSP20, brain-derived neurotrophic factor (BDNF), and the tropomyosin receptor kinase B (TrkB) ratio, PE rehabilitation significantly attenuated brain contusi...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
A Novel Five-Node Feed-Forward Loop Unravels miRNA-Gene-TF Regulatory Relationships in Ischemic Stroke
AbstractThe complex and interlinked cascade of events regulated by microRNAs (miRNAs), transcription factors (TF), and target genes highlight the multifactorial nature of ischemic stroke pathology. The complexity of ischemic stroke requires a wider assessment than the existing experimental research that deals with only a few regulatory components. Here, we assessed a massive set of genes, miRNAs, and transcription factors to build a miRNA-gene-transcription factor regulatory network to elucidate the underlying post-transcriptional mechanisms in ischemic stroke. Feed-forward loops (three-node, four-node, and novel five-node...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
Folic Acid Exerts Post-Ischemic Neuroprotection In Vitro Through HIF-1 α Stabilization
AbstractThe constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis
In this study, we used fluid percussion injury in rats to simulate mild TBI. For rats, we used both passive avoidance learning and the Y-maze tests to evaluate cognitive function. We investigated whether PE rehabilitation attenuated cognitive deficits in rats with TBI and determined the contribution of hippocampal and cortical expression of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery. In addition to increasing hippocampal and cortical expression of HSP20, brain-derived neurotrophic factor (BDNF), and the tropomyosin receptor kinase B (TrkB) ratio, PE rehabilitation significantly attenuated brain contusi...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
A Novel Five-Node Feed-Forward Loop Unravels miRNA-Gene-TF Regulatory Relationships in Ischemic Stroke
AbstractThe complex and interlinked cascade of events regulated by microRNAs (miRNAs), transcription factors (TF), and target genes highlight the multifactorial nature of ischemic stroke pathology. The complexity of ischemic stroke requires a wider assessment than the existing experimental research that deals with only a few regulatory components. Here, we assessed a massive set of genes, miRNAs, and transcription factors to build a miRNA-gene-transcription factor regulatory network to elucidate the underlying post-transcriptional mechanisms in ischemic stroke. Feed-forward loops (three-node, four-node, and novel five-node...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
Folic Acid Exerts Post-Ischemic Neuroprotection In Vitro Through HIF-1 α Stabilization
AbstractThe constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
Possible Involvement of PI3-K/Akt-Dependent GSK-3 β Signaling in Proliferation of Neural Progenitor Cells After Hypoxic Exposure
AbstractWe previously demonstrated that proliferation of endogenous neural progenitor cells is enhanced by cerebral ischemia and that phosphatidylinositol 3-kinase (PI3-K)/Akt-dependent glycogen synthase kinase (GSK)-3 β signaling is involved in ischemia-induced neurogenesis. It is important to learn more about the regulation of proliferation and differentiation of neural progenitor cells under ischemic conditions, as such knowledge that may serve as the basis for the development of new therapeutic approaches for stroke. However, it remains to be addressed whether a change in that signaling pathway is induced in neural pr...
Source: Molecular Neurobiology - July 6, 2018 Category: Neurology Source Type: research
Monogenic, Polygenic, and MicroRNA Markers for Ischemic Stroke
AbstractIschemic stroke (IS) is a leading disease with high mortality and disability, as well as with limited therapeutic window. Biomarkers for earlier diagnosis of IS have long been pursued. Family and twin studies confirm that genetic variations play an important role in IS pathogenesis. Besides DNA mutations found previously by genetic linkage analysis for monogenic IS (Mendelian inheritance), recent studies using genome-wide associated study (GWAS) and microRNA expression profiling have resulted in a large number of DNA and microRNA biomarkers in polygenic IS (sporadic IS), especially in different IS subtypes and imag...
Source: Molecular Neurobiology - June 8, 2018 Category: Neurology Source Type: research
Deep Sequencing Reveals Uncharted Isoform Heterogeneity of the Protein-Coding Transcriptome in Cerebral Ischemia
AbstractGene expression in cerebral ischemia has been a subject of intense investigations for several years. Studies utilizing probe-based high-throughput methodologies such as microarrays have contributed significantly to our existing knowledge but lacked the capacity to dissect the transcriptome in detail. Genome-wide RNA-sequencing (RNA-seq) enables comprehensive examinations of transcriptomes for attributes such as strandedness, alternative splicing, alternative transcription start/stop sites, and sequence composition, thus providing a very detailed account of gene expression. Leveraging this capability, we conducted a...
Source: Molecular Neurobiology - June 3, 2018 Category: Neurology Source Type: research
