Frontiers in neuroscience
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Frontiers in neuroscience · Jan 2019
ReviewMechanisms of Immune Activation by c9orf72-Expansions in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with overlapping pathomechanisms, neurobehavioral features, and genetic etiologies. Individuals diagnosed with either disorder exhibit symptoms within a clinical spectrum. Symptoms of ALS involve neuromusculature deficits, reflecting upper and lower motor neurodegeneration, while the primary clinical features of FTD are behavioral and cognitive impairments, reflecting frontotemporal lobar degeneration. ⋯ This review highlights the current understanding of the cellular, proteomic and genetic substrates through which G4C2 HREs may elicit detrimental immune activity, facilitating region-specific neurodegeneration in C9orf72 mediated ALS/FTD. We in particular emphasize interactions between intracellular pathways induced by C9orf72 expansions and innate immune inflammasome complexes, intracellular receptors responsible for eliciting inflammation in response to cellular stress. A further understanding of the intricate, reciprocal relationship between the cellular and molecular pathologies resulting from C9orf72 HREs and immune activation may yield novel therapeutics for ALS/FTD, which currently have limited treatment strategies.
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Frontiers in neuroscience · Jan 2019
ReviewCD200-CD200R Interaction: An Important Regulator After Stroke.
The high mortality and morbidity rate of stroke is a chronic problem that plagues human society. The activation of microglia is one of the principal reasons why neuroinflammation induces cerebral dysfunction. Because of their vital functions in the regulation of neuroinflammation, microglia constitute an important target for stroke. ⋯ The role of crosstalk of CD200-CD200R inhibitory immune ligand receptors in immune regulation will also be illustrated. Thus, we will see how poststroke injury can be influenced by the CD200-CD200R crosstalk. Finally, we will discuss the possibility of clinical application of the result of CD200-CD200R interaction to manage neuroinflammatory injury after stroke.
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Frontiers in neuroscience · Jan 2019
ReviewVagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations.
Over the last several decades, vagus nerve stimulation (VNS) has evolved from a treatment for select neuropsychiatric disorders to one that holds promise in treating numerous inflammatory conditions. Growing interest has focused on the use of VNS for other indications, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury. ⋯ In this review, we discuss these important considerations and how a combination of clinically relevant stimulation parameters can be used to achieve beneficial therapeutic results in pre-clinical studies of sub-acute to chronic VNS, and provide a practical guide for performing this work in rodent models. Finally, by integrating clinical and pre-clinical research, we present indeterminate issues as opportunities for future research.
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Frontiers in neuroscience · Jan 2019
Single Sessions of High-Definition Transcranial Direct Current Stimulation Do Not Alter Lower Extremity Biomechanical or Corticomotor Response Variables Post-stroke.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate cortical activity. However, measured effects on clinically relevant assessments have been inconsistent, possibly due to the non-focal dispersion of current from traditional two electrode configurations. High-definition (HD)-tDCS uses a small array of electrodes (N = 5) to improve targeted current delivery. ⋯ A single session of anodal or cathodal HD-tDCS delivered to a standardized ipsilesional area of the motor cortex does not appear to alter gait kinematics or corticomotor response post-stroke. Repeated sessions and individualized delivery of HD-tDCS may be required to induce beneficial plastic effects. Contralesional stimulation should also be investigated due to the altered interactions between the cerebral hemispheres post-stroke.
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Frontiers in neuroscience · Jan 2019
Converging and Differential Brain Phospholipid Dysregulation in the Pathogenesis of Repetitive Mild Traumatic Brain Injury and Alzheimer's Disease.
Repetitive mild traumatic brain injury (rmTBI) is a major epigenetic risk factor for Alzheimer's disease (AD). The precise nature of how rmTBI leads to or precipitates AD pathology is currently unknown. Numerous neurological conditions have shown an important role for dysfunctional phospholipid metabolism as a driving factor for the pathogenesis of neurodegenerative diseases. ⋯ This study demonstrates some overlapping and diverse phospholipid profiles in rmTBI and AD models. Future studies are required to corroborate our findings in human post-mortem tissue. Investigation of secondary mechanisms triggered by aberrant downstream alterations in bioactive metabolites of these phospholipids, and their modulation at the appropriate time-windows of opportunity could help facilitate development of novel therapeutic strategies to ameliorate the neurodegenerative consequences of rmTBI or the potential triggering of AD pathogenesis by rmTBI.