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Source: Molecular Neurobiology
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Total 278 results found since Jan 2013.
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
Neutrophil Extracellular Traps Exacerbate Ischemic Brain Damage
AbstractMost acute strokes are ischemic, and subsequent neuroinflammation promotes further damage leading to cell death but also plays a beneficial role by promoting cellular repair. Neutrophils are forerunners to brain lesions after ischemic stroke and exert elaborate functions. While neutrophil extracellular traps (NETs) possess a fundamental antimicrobial function within the innate immune system under physiological circumstances, increasing evidence indicates that NETosis, the release process of NETs, occurs in the pathogenic process of stroke. In this review, we focus on the processes of NET formation and clearance, th...
Source: Molecular Neurobiology - November 8, 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
Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders
AbstractMesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton ’s jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-...
Source: Molecular Neurobiology - October 29, 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
Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases
This article mainly focu ses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new ...
Source: Molecular Neurobiology - October 15, 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
NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia
In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed ligh t on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia.
Source: Molecular Neurobiology - October 1, 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
Long Non-coding RNA PVT1 Inhibits miR-30c-5p to Upregulate Rock2 to Modulate Cerebral Ischemia/Reperfusion Injury Through MAPK Signaling Pathway Activation
AbstractLong non-coding RNAs (lncRNAs) play a key role in a variety of disease processes. Plasmacytoma variant translocation 1 (PVT1), a lncRNA, is known to regulate cell functions and play a key role in the pathogenesis of many malignant tumors. The function and molecular mechanisms of lncRNA-PVT1 in cerebral ischemia remain unknown. Real-time PCR (qRT-PCR) was used to detect lncRNA-PVT1 and microRNA-30c-5p (miR-30c-5p) expression in the brain tissues of mice underwent middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen –glucose deprivation/reperfusion (OGD/R)-treated mouse primary brain neurons. Gain- or l...
Source: Molecular Neurobiology - August 26, 2021 Category: Neurology Source Type: research
