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Source: Molecular Neurobiology
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Total 171 results found since Jan 2013.
The Two-Pore Domain Potassium Channel TREK-1 Promotes Blood –Brain Barrier Breakdown and Exacerbates Neuronal Death After Focal Cerebral Ischemia in Mice
This study used TREK-1-deficient mice to directly investigate the role of TREK-1 after focal cerebral ischemia. First, immunofluorescence assays in the mouse cerebral cortex indicated that TREK-1 expression was mostly abundant in astrocytes, neurons, and oligodendrocyte precursor cells but was low in myelinating oligodendrocytes, microglia, or endothelial cells. TREK-1 deficiency did not affect brain weight and morphology or the number of neurons, astrocytes, or microglia but did increase glial fibrillary acidic protein (GFAP) expression in astrocytes of the cerebral cortex. The anatomy of the major cerebral vasculature, n...
Source: Molecular Neurobiology - January 24, 2022 Category: Neurology Source Type: research
Sevoflurane Offers Neuroprotection in a Cerebral Ischemia/Reperfusion Injury Rat Model Through the E2F1/EZH2/TIMP2 Regulatory Axis
This study is aimed to delineate the molecular mechanistic actions by which sevoflurane protects against cerebral I/R injury. A rat model of cerebral I/R injury was established and pre-treated with sevoflurane, in which hippocampal neuron apoptosis was found to be repressed and the level of E2F transcription factor 1 (E2F1) was observed to be down-regulated. Then, the up-regulated expression of E2F1 was validated in rats with cerebral I/R injury, responsible for stimulated neuron apoptosis. Further, the binding of E2F1 to enhancer of zeste homolog 2 (EZH2) and EZH2 to tissue inhibitor of metalloproteinases-2 (TIMP2) was id...
Source: Molecular Neurobiology - January 22, 2022 Category: Neurology Source Type: research
COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion
In conclusion, PGE2 was positively correlated with ferroptosis, inhibition of ferroptosis induced by cerebral I/R can inactivate COX-2/PGE2 pathway, and PGE2 inhibited ferroptosis induced by cerebral I/R, possibly via PGE2 receptor 3 and PGE2 receptor 4.Graphical abstractInhibition of ferroptosis inactivates the COX-2/PGE2 pathway. Cerebral ischemia reperfusion injury induces the secretion of PGE2. After the inhibition of ferroptosis by Fer-1, the expression of cyclooxygenases (COX-1 and COX-2) decreased, and PGE2 synthases cPGES, mPGES-1, and mPGES-2 were also reduced. At the same time, the PGE2 degradation enzyme 15-PGDH...
Source: Molecular Neurobiology - January 10, 2022 Category: Neurology Source Type: research
Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning
In this study, we investigated astrocyte-specific MCT4 in motor learning and neuroplasticity of the M1 primary motor cortex using a cell-type specific shRNA knockdown of MCT4. Knockdown of astrocyte-specific MCT4 resulted in impaired motor performance and learning on the accelerating rotarod. In addition, MCT4 knockdown was associated with a reduction of neuronal dendritic spine density and spine width and decreased protein expression of PSD95, Arc, and cFos. Using near-infrared –conjugated 2-deoxyglucose uptake as a surrogate marker for neuronal activity, MCT4 knockdown was also associated with decreased neuronal activi...
Source: Molecular Neurobiology - November 25, 2021 Category: Neurology Source Type: research
Phosphodiesterase 10A Is a Critical Target for Neuroprotection in a Mouse Model of Ischemic Stroke
AbstractPhosphodiesterase 10A (PDE10A) hydrolyzes adenosine 3 ′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP). It is highly expressed in the striatum. Recent evidence implied that PDE10A may be involved in the inflammatory processes following injury, such as ischemic stroke. Its role in ischemic injury was unknown. Here in, we exposed mice to 90 or 30-min middle cerebral artery occlusion, followed by the delivery of the highly selective PDE10A inhibitor TAK-063 (0.3 mg/kg or 3 mg/kg) immediately after reperfusion. Animals were sacrificed after 24 or 72 h, respectively. Both TAK-0...
Source: Molecular Neurobiology - November 4, 2021 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
Ferrostatin-1 Alleviates White Matter Injury Via Decreasing Ferroptosis Following Spinal Cord Injury
AbstractSpinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role...
Source: Molecular Neurobiology - October 12, 2021 Category: Neurology Source Type: research
Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence
AbstractEfforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused o...
Source: Molecular Neurobiology - October 4, 2021 Category: Neurology Source Type: research
PAF Receptor Inhibition Attenuates Neuronal Pyroptosis in Cerebral Ischemia/Reperfusion Injury
AbstractIschemic stroke is an inflammation-related disease, during which process activation of NLRP3 inflammasome and subsequent pyroptosis play crucial roles. Platelet-activating factor (PAF) is a potent phospholipid regulator of inflammation which exerts its effect via binding specific PAF receptor (PAFR). However, whether PAFR contributes to pyroptosis during ischemia/reperfusion (I/R) injury remains to be elucidated. To explore the underlying effect of PAFR on ischemic stroke from the perspective of pyroptosis, mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) injury and primary cultures of m...
Source: Molecular Neurobiology - September 25, 2021 Category: Neurology Source Type: research
Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke
AbstractIschemic stroke is the third leading cause of mortality worldwide, but its medical management is still limited to the use of thrombolytics as a lifesaving option. Multiple molecular deregulations of the protein kinase family occur during the period of ischemia/reperfusion. However, experimental studies have shown that alterations in the expression of essential protein kinases and their pharmacological modulation can modify the neuropathological milieu and hasten neurophysiological recovery. This review highlights the role of key protein kinase members and their implications in the evolution of stroke pathophysiolog...
Source: Molecular Neurobiology - September 22, 2021 Category: Neurology Source Type: research
Application of Metabolomics to the Discovery of Biomarkers for Ischemic Stroke in the Murine Model: a Comparison with the Clinical Results
AbstractIschemic stroke (IS) is a major cause of mortality and disability worldwide. However, the pathogenesis of IS remains unknown, and methods for early prediction and diagnosis of IS are lacking. Metabolomics can be applied to biomarker discovery and mechanism exploration of IS by exploring metabolic alterations. In this review, 62 IS metabolomics studies in the murine model published from January 2006 to December 2020 in the PubMed and Web of Science databases were systematically reviewed. Twenty metabolites (e.g., lysine, phenylalanine, methionine, tryptophan, leucine, lactate, serine, N-acetyl-aspartic acid, and glu...
Source: Molecular Neurobiology - September 17, 2021 Category: Neurology Source Type: research
Phenothiazine Inhibits Neuroinflammation and Inflammasome Activation Independent of Hypothermia After Ischemic Stroke
In conclusion, C + P treatment conferred neuroprotection in stroke by suppressing neuroinflammation and NLRP3 inflammasome activation. The present study suggests that JAK2/STAT3/p38/HIF-1α/FoxO1 are vital regulators and potential targets for efficacious therapy following ischemic stroke.
Source: Molecular Neurobiology - August 29, 2021 Category: Neurology Source Type: research
Post Stroke Safinamide Treatment Attenuates Neurological Damage by Modulating Autophagy and Apoptosis in Experimental Model of Stroke in Rats
AbstractExploring and repurposing a drug have become a lower risk alternative. Safinamide, approved for Parkinson ’s disease, has shown neuroprotection in various animal models of neurological disorders. The present study aimed to explore the potential of safinamide in cerebral ischemia/reperfusion (I/R) in rats. Sprague–Dawley rats were used in middle cerebral artery occlusion model of stroke. The effectiv e dose of safinamide was selected based on the results of neurobehavioral parameters and reduction in infarct size assessed 24 h post-reperfusion. For sub-acute study, the treatment with effective dose was extended...
Source: Molecular Neurobiology - August 28, 2021 Category: Neurology Source Type: research
Effect of Anti-inflammatory Treatment with AMD3100 and CX3CR1 Deficiency on GABAA Receptor Subunit and Expression of Glutamate Decarboxylase Isoforms After Stroke
AbstractFollowing stroke, attenuation of detrimental inflammatory pathways might be a promising strategy to improve long-term outcome. In particular, cascades driven by pro-inflammatory chemokines interact with neurotransmitter systems such as the GABAergic system. This crosstalk might be of relevance for mechanisms of neuronal plasticity, however, detailed studies are lacking. The purpose of this study was to determine if treatment with 1,1 ′-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and partial allosteric agonist to CXCR7 ...
Source: Molecular Neurobiology - August 20, 2021 Category: Neurology Source Type: research
