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Epigenetic Restoration of Voltage ‐gated Potassium Channel Kv1.2 Alleviates Nerve Injury‐induced Neuropathic Pain
AbstractVoltage ‐gated potassium channels (Kv) are important regulators of neuronal excitability for its role of regulating resting membrane potential and repolarization. Recent studies show that Kv channels participate in neuropathic pain, but the detailed underlying mechanisms are far from being clear. In the c urrent study, we used siRNA, miR‐137 agomir and antagomir to regulate the expression of Kv1.2 in spinal cord and dorsal root ganglia (DRG) of naïve and chronic constriction injury (CCI) rats. Kv currents and neuron excitability in DRG neurons were examined by patch‐clamp whole‐cell recording to verify the...
Source: Journal of Neurochemistry - July 2, 2020 Category: Neuroscience Authors: Jingjing Zhang, Lina Rong, Jinping Shao, Yidan Zhang, Yaping Liu, Sen Zhao, Lei Li, Wenli Yu, Mengya Zhang, Xiuhua Ren, Qingzan Zhao, Changlian Zhu, Huan Luo, Weidong Zang, Jing Cao Tags: ORIGINAL ARTICLE Source Type: research

Evaluation of the Effect of (S)-3,4-Dicarboxyphenylglycine as a Metabotropic Glutamate Receptors Subtype 8 Agonist on Thermal Nociception Following Central Neuropathic Pain.
Conclusions: The results revealed that activation of mGluR8 in PAG is not capable of improving the thermal hyperalgesia threshold. Based on the decreased expression of mGluR8 after SCI induced by clip compression injury and its significant increase after treatment of siRNA against mGluR8, this method might still hold promise as an effective treatment of neuropathic pain. It can be concluded that increased expression of mGluR8 is due to the fact that DCPG prevents the death of neurons that express these receptors. PMID: 32460469 [PubMed - as supplied by publisher]
Source: Asian Spine Journal - May 29, 2020 Category: Orthopaedics Tags: Asian Spine J Source Type: research

MicroRNA ‐22‐3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5
AbstractCell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR ‐22‐3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12‐min occlusion of the aortic arch followed by 48‐h reperfusion, with L4...
Source: Journal of Neurochemistry - May 13, 2020 Category: Neuroscience Authors: Hua Fang, Miao Yang, Qin Pan, Hon ‐Ling Jin, Hua‐Feng Li, Ru‐Rong Wang, Quan‐Yun Wang, Jian‐Ping Zhang Tags: ORIGINAL ARTICLE Source Type: research

The inhibiting role of periaqueductal gray metabotropic glutamate receptor subtype 8 in a rat model of central neuropathic pain.
In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, in a model of chronic central neuropathic pain in male rats. We used a spinal cord contusion method (T6-T8) for the induction of chronic central neuropathic pain.Male Wistar rats were randomly assigned to 5 equal groups (n = 10 per group). Clips compression injury model was used to induce chronic central neuropathic pain. Three weeks after spinal cord injury DCPG, siRNA and normal saline were administered intra-ventrolaterally to the periaqueductal gray (PAG) regi...
Source: Neurological Research - April 6, 2020 Category: Neurology Tags: Neurol Res Source Type: research

The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway.
Abstract Spinal cord injury (SCI) is a devastating disease associated with locomotor function impair. The limited regenerative capability of the neural axon is one of the major factors that hinders the recovery of SCI. To enhance the regenerative ability of neuron is a promising strategy that repairs SCI. We previously proved miR-17-5p could target Signal Transducer and Activator of Transcription 3 (STAT3) in primary sensory neuron. We speculated that miR-17-5p was the miRNA that targets STAT3. The Dual-luciferase reporter assay indicated miR-17-5p could bind the 3'UTR of STAT3 mRNA. The RT-qPCR and Western blot a...
Source: Molecular Biology Reports - February 23, 2020 Category: Molecular Biology Authors: Zhang L, Wang Z, Li B, Xia Z, Wang X, Xiu Y, Zhang Z, Chen C, Song H, Li W, Yu M, Zhang M, Wang K, Guo X, Ren L, Wang T Tags: Mol Biol Rep Source Type: research

A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration Cell Biology
Glial signals are known to inhibit axonal regeneration and functional recovery after mammalian central nervous system trauma, including spinal cord injury. Such signals include membrane-associated proteins of the oligodendrocyte plasma membrane and astrocyte-derived, matrix-associated proteins. Here, using cell lines and primary cortical neuron cultures, recombinant protein expression, immunoprecipitation and immunoblot assays, transmission EM of exosomes, and axon regeneration assays, we explored the secretion and activity of the myelin-associated neurite outgrowth inhibitor Nogo-A and observed exosomal release of a 24-kD...
Source: Journal of Biological Chemistry - February 20, 2020 Category: Chemistry Authors: Yuichi Sekine, Jane A. Lindborg, Stephen M. Strittmatter Tags: Editors ' Picks Source Type: research

The Roles of Chemokine (C-X-C motif) Ligand 13 in Spinal Cord Ischemia-Reperfusion Injury in Rats.
In this study, we studied the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in a rat model of SCII. We examined the time course and cellular distribution of CXCL13 protein in rats after SCII. The effects of siRNA targeting CXCL13 or C-X-C chemokine receptor type 5 (CXCR5) in SCII were also investigated. Neurological function, histological assessment, and disruption of the blood-spinal cord barrier (BSCB) were evaluated. The expression levels of CXCL13, CXCR5, phosphorylated extracellular signal-regulated kinase (p-ERK), caspase-3, interleukin 6 (IL-6), TNF-α, and IL-1β were determined. We found that SCII resulted in...
Source: Brain Research - October 3, 2019 Category: Neurology Authors: Chen F, Li X, Li Z, Zhou Y, Qiang Z, Ma H Tags: Brain Res Source Type: research

Receptor for Activated C Kinase 1 Mediates the Chronic Constriction Injury-induced Neuropathic Pain in the Rats’ Peripheral and Central Nervous System
In this study, the biological effects and mechanisms of RACK1 contributes to the pathogenesis of chronic constriction injury (CCI)-induced neuropathic pain were investigated. By western blot and staining, we found that RACK1 protein changed in dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons except glial cells after CCI. Especially, RACK1 was co-located with IB4-, CGRP-positive neurons, suggesting it was related to integrate nociceptive information from the primary afferents in DRG. The successful establishment of CCI models also directly led to mechanical allodynia and heat hyperalgesia, which could be rev...
Source: Neuroscience Letters - September 4, 2019 Category: Neuroscience Source Type: research

ASAP Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury
ACS NanoDOI: 10.1021/acsnano.9b01892
Source: ACS Nano - August 29, 2019 Category: Nanotechnology Authors: Shaowei Guo †‡, Nisim Perets§, Oshra Betzer?, Shahar Ben-Shaul†, Anton Sheinin§, Izhak Michaelevski?, Rachela Popovtzer?, Daniel Offen§#, and Shulamit Levenberg*† Source Type: research

Nrf2/HO-1 signaling pathway participated in the protection of hydrogen sulfide on neuropathic pain in rats.
Abstract Neuropathic pain is evoked by aberrant sensory processing in the peripheral or central nervous system, which is characterized by persistent pain, tactile allodynia, or hyperalgesia. Neuroinflammation is associated with the initiation and maintenance of persistent pain in both the peripheral and central nervous systems. Hydrogen sulfide plays important regulatory roles in different physiological and pathological conditions. Therefore, we investigated the effect of hydrogen sulfide on allodynia, hyperalgesia and cytokine release in rats with neuropathic pain and the related regulatory mechanism. Neuropathic...
Source: International Immunopharmacology - July 16, 2019 Category: Allergy & Immunology Authors: Chen H, Xie K, Chen Y, Wang Y, Wang Y, Lian N, Zhang K, Yu Y Tags: Int Immunopharmacol Source Type: research

Exosomes loaded with PTEN siRNA leads to functional recovery after complete transection of the spinal cord by specifically targeting the damaged area
ConclusionMSC-exo were extracted from Human bone marrow mesenchymal stem cells. All rats had complete transection of the spinal cord. MSC-exo were loaded with co-incubation together with siRNA for PTEN conjugated to cholesterol. The MSC-exo were given by intranasal administration 1-4 hours post-SCI.
Source: Cytotherapy - May 24, 2019 Category: Cytology Source Type: research

i-Fect used to Study Angiogenesis in Brain Injury
This study revealed that LDHA, which is a known damage marker, promotes CNS-specific angiogenesis. LDHA-mediated angiogenesis depends on vimentin on the surface of vascular endothelial cells. The work described here proposes a novel mechanism by which neurodegeneration drives angiogenesis in the CNS.A mixture of ouri-FectTM and LDHA siRNA, in this study, were directly injected into mice cortexes: Hsiaoyun Lin, Rieko Muramatsu, Noriko Maedera, Hiroto Tsunematsu, Machika Hamaguchi, Yoshihisa Koyama, Mariko Kuroda, Kenji Ono, Makoto Sawada, Toshihide Yamashita.Extracellular Lactate Dehydrogenase A Release ...
Source: siRNA and DsiRNA Transfection Efficiency - May 9, 2019 Category: Neuroscience Tags: Angiogenesis iFect TBI traumatic brain injury Source Type: news

HDAC2, but Not HDAC1, Regulates Kv1.2 Expression to Mediate Neuropathic Pain in CCI Rats
In this study we established a chronic constrictive injury (CCI) model and used western blot, quantitative real-time PCR, immunostaining, intrathecal injection, and siRNA methods to explore which HDAC subunit is involved in regulating Kv1.2 expression to mediate NPP. Our results demonstrated that nerve injury led to upregulation of HDAC1 expression in the DRG, and of HDAC2 in the DRG and spinal cord. Double-labeling immunofluorescence histochemistry showed that Kv1.2 principally co-localized with HDAC2, but not HDAC1, in NF200-positive large neurons of the DRG. Intrathecal injection with the HDAC inhibitor, suberoylanilide...
Source: Neuroscience - April 24, 2019 Category: Neuroscience Source Type: research

MicroRNA-448 inhibits the regeneration of spinal cord injury through PI3K/AKT/Bcl-2 axis.
CONCLUSIONS: MicroRNA-448 is upregulated after SCI, which may be involved in the regenerative process of spinal motor nerves by regulating PI3K/AKT/Bcl-2 axis. PMID: 31002121 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

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