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Loss of Estrogen Efficacy Against Hippocampus Damage in Long-Term OVX Mice Is Related to the Reduction of Hippocampus Local Estrogen Production and Estrogen Receptor Degradation
AbstractPostmenopausal women experience a higher risk for neurodegenerative diseases, including cognitive impairment and ischemic stroke. Many preclinical studies have indicated that estrogen replacement therapy (ERT) may provide protective effects against these neurological diseases. However, the results of Women ’s Health Initiative (WHI) studies have led to the proposal of “critical period hypothesis,” which states that there is a precise window of opportunity for administering beneficial hormone therapy following menopause. However, the underlying molecular mechanisms require further characterizatio n. Here, we e...
Source: Molecular Neurobiology - June 14, 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

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

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

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

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

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

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

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