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Peripheral Nerve Injury

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41. Chemogenetic Enhancement of Axon Regeneration Following Peripheral Nerve Injury in the SLICK-A Mouse Full Text available with Trip Pro

Chemogenetic Enhancement of Axon Regeneration Following Peripheral Nerve Injury in the SLICK-A Mouse The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre-recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired (...) and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i.p.), or were untreated controls. Two weeks after injury, the lengths of YFP+ axon profiles were measured in nerves harvested from euthanized animals. Compared to untreated controls, regenerating axon lengths were not significantly longer in mice treated only once with CNO, but they were more than three times longer in mice receiving CNO repeatedly. Based on results

2018 Brain sciences

42. Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury Full Text available with Trip Pro

Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury The neural regeneration process is driven by a wide range of molecules and pathways. Adherens junctions are critical cellular junctions for the integrity of peripheral nerves. However, few studies have systematically characterized the transcript changes in the adherens junction pathway following injury. In this study, a rat model of sciatic nerve crush injury was established by forceps. Deep (...) of these genes were upregulated in the sciatic nerve stump following peripheral nerve injury, except for CTNNA2, which was downregulated. Our findings reveal the dynamic changes of key molecules in adherens junctions and in remodeling of adherens junctions. These key genes provide a reference for the selection of clinical therapeutic targets for peripheral nerve injury.

2018 Neural Regeneration Research

43. miR-129 controls axonal regeneration via regulating insulin-like growth factor-1 in peripheral nerve injury Full Text available with Trip Pro

miR-129 controls axonal regeneration via regulating insulin-like growth factor-1 in peripheral nerve injury The microenvironment of peripheral nerve regeneration consists of multiple neurotrophic factors, adhesion molecules, and extracellular matrix molecules, secreted by unique glial cells in the peripheral nerve system (PNS)-Schwann cell (SCs). Following peripheral nerve injury (PNI), local IGF-1 production is upregulated in SCs and denervated muscle during axonal sprouting and regeneration (...) . Regulation of IGF-1/IGF-1R signaling is considered as a potentially targeted therapy of PNI. We previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection. The present work focused on the role of miR-129 in regulation of IGF-1 signaling after sciatic nerve injury. The temporal change profile of the miR-129 expression was negatively correlated with the IGF-1 expression in proximal nerve stump and dorsal root ganglion (DRG) following sciatic nerve transection

2018 Cell death & disease

44. Temporal changes in macrophage phenotype after peripheral nerve injury Full Text available with Trip Pro

Temporal changes in macrophage phenotype after peripheral nerve injury Macrophages play a key role in peripheral nerve repair and demonstrate complex phenotypes that are highly dependent on microenvironmental cues.We determined temporal changes in macrophage gene expression over time using RNA sequencing after fluorescence-activated cell sorting (FACS) macrophage populations from injured peripheral nerve. We identified key upstream regulators and dominant pathways using ingenuity pathway (...) analysis and confirmed these changes with NanoString technology. We then investigate the effects of extreme polarizers of macrophage phenotype (IL4 and IFNγ) on nerve regeneration. We determined macrophage gene expression in vivo at the site of peripheral nerve injury with NanoString technology, and assessed recovery from sciatic nerve injury by cranial tibial muscle weights and retrograde labeling motor neurons in mice with deletion of IL4 or IFNγ receptors.We demonstrate that IL4R and IFNγR deletions

2018 Journal of neuroinflammation

45. Peripheral nerve injury with Nexplanon removal: case report and review of the literature Full Text available with Trip Pro

Peripheral nerve injury with Nexplanon removal: case report and review of the literature Implantable devices offer convenient, long-acting, and reversible contraception. Injury to the peripheral nerves and blood vessels have been reported as rare complications of implantation and extraction.We present a case of ulnar nerve injury in a 21-year-old woman from attempted in-office removal of a deeply implanted Nexplanon® device. The injury resulted in an ulnar nerve palsy requiring surgical (...) exploration, neuroma excision, and sural nerve cable grafting.In-office attempts to remove contraceptive implants that are deep or have migrated can cause iatrogenic nerve injury. Devices that are non-palpable, deep, or migrated should be imaged before formal surgical exploration and removal. Any patient with neurologic symptoms after placement or after attempted removal requires prompt diagnosis and referral to a peripheral nerve surgeon.

2018 Contraception and Reproductive Medicine

46. Peripheral Nerve Injury Induces Dynamic Changes of Tight Junction Components Full Text available with Trip Pro

Peripheral Nerve Injury Induces Dynamic Changes of Tight Junction Components Tight junctions seal off physical barriers, regulate fluid and solute flow, and protect the endoneurial microenvironment of the peripheral nervous system. Physical barriers in the peripheral nervous system were disrupted after nerve injury. However, the dynamic changes of tight junction components after peripheral nerve injury have not been fully determined yet. In the current study, by using previously obtained deep (...) sequencing outcomes and bioinformatic tools, we found that tight junction signaling pathway was activated after peripheral nerve injury. The investigation of the temporal expression patterns of components in tight junction signaling pathway suggested that many claudin family members were down-regulated after nerve injury. Moreover, we examined the effects of matrix metalloproteinases 7 and 9 (MMP7 and MMP9) on tight junction genes both in vitro and in vivo and found that MMP7 and MMP9 modulated

2018 Frontiers in physiology

47. Dental pulp-derived stem cells can counterbalance peripheral nerve injury-induced oxidative stress and supraspinal neuro-inflammation in rat brain Full Text available with Trip Pro

Dental pulp-derived stem cells can counterbalance peripheral nerve injury-induced oxidative stress and supraspinal neuro-inflammation in rat brain Previously, we reported the successful regeneration of injured peripheral nerves using human dental pulp stem cells (DPSCs) or differentiated neuronal cells from DPSCs (DF-DPSCs) in a rat model. Here, we attempted to evaluate oxidative stress and supraspinal neuro-inflammation in rat brain after sciatic nerve injury (SNI). We divided our experimental (...) was lower at 2 weeks, while it gradually increased at 8 and 12 weeks after surgery in the SNI DPSCs and DF-DPSCs groups. Similarly, SNI DPSCs had a high expression of pAMPK, SIRT1 and NFkB at the onset of SNI. However, 12 weeks after surgery, pAMPK and SIRT1 expression levels were higher and NFkB was down-regulated in both DPSCs and DF-DPSCs compared to the control group. Finally, we concluded that DPSCs responded early and more efficiently than DF-DPSCs to counterbalance peripheral nerve injury (PNI

2018 Scientific reports

48. Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury Full Text available with Trip Pro

Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury Neuroinflammation accompanies neural trauma and most neurological diseases. Axotomy in the peripheral nervous system (PNS) leads to dramatic changes in the injured neuron: the cell body expresses a distinct set of genes known as regeneration-associated genes, the distal axonal segment degenerates and its debris is cleared, and the axons in the proximal segment form growth cones and extend (...) neurites. These processes are orchestrated in part by immune and other non-neuronal cells. Macrophages in ganglia play an integral role in supporting regeneration. Here, we explore further the molecular and cellular components of the injury-induced immune response within peripheral ganglia.Adult male wild-type (WT) and Ccr2 -/- mice were subjected to a unilateral transection of the sciatic nerve and axotomy of the superior cervical ganglion (SCG). Antibody arrays were used to determine the expression

2018 Journal of neuroinflammation

49. Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury Full Text available with Trip Pro

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury Puerarin is a major active ingredient of the traditional Chinese plant medicine, Radix Puerariae, and commonly used in the treatment of myocardial and cerebral ischemia. However, the effects of puerarin on neuropathic pain are still unclear. In this study, a neuropathic pain animal model was created by partial sciatic nerve ligation. Puerarin (30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days (...) receptor potential ankyrin 1 (Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury. These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.

2018 Neural Regeneration Research

50. iTRAQ-based proteomics profiling of Schwann cells before and after peripheral nerve injury Full Text available with Trip Pro

iTRAQ-based proteomics profiling of Schwann cells before and after peripheral nerve injury Schwann cells (SCs) have a wide range of applications as seed cells in the treatment of nerve injury during transplantation. However, there has been no report yet on kinds of proteomics changes that occur in Schwann cells before and after peripheral nerve injury.Activated Schwann cells (ASCs) and normal Schwann cells (NSCs) were obtained from adult Wistar rat sciatic nerves. After immunofluorescence (...) were consistent with the proteomics data obtained by Western blot analysis.GPNMB, ENPP3, GFPT2, and other proteins may play an important role in the repair of peripheral nerve injury. This study may provide new insights into changes in SCs after peripheral nerve injury.

2018 Iranian journal of basic medical sciences

51. Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition Full Text available with Trip Pro

Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity (...) the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

2018 Experimental & molecular medicine

52. Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury Full Text available with Trip Pro

Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential (...) crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation

2018 Journal of tissue engineering and regenerative medicine

53. The Whole Transcriptome Involved in Denervated Muscle Atrophy Following Peripheral Nerve Injury Full Text available with Trip Pro

The Whole Transcriptome Involved in Denervated Muscle Atrophy Following Peripheral Nerve Injury Peripheral nerve injury (PNI) usually leads to progressive muscle atrophy and poor functional recovery. Previous studies have demonstrated that non-coding ribonucleic acid (ncRNA) is a key regulator of muscle atrophy and beneficial for the treatment of PNI. We aimed to analyze the whole transcriptome involved in denervated muscle atrophy after PNI. Animal models of sciatic nerve injury were assessed (...) at 0 (control group), 1, 2, 4, and 8 weeks after injury. The expression patterns in the whole transcriptome in the gastrocnemius muscle were profiled using RNA sequencing at each time point and compared to that obtained in the control group. Six-hundred and sixty-four long non-coding RNAs, 671 microRNAs, 236 circular RNAs, and 12,768 messenger RNAs (mRNAs) were differentially expressed (DE) after injury. Changes in some of the DE ncRNAs and mRNAs were validated using quantitative polymerase chain

2018 Frontiers in molecular neuroscience

54. Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model Full Text available with Trip Pro

Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning (...) the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control) or BoNT/B (5 or 7.5 pg/mouse) into the injured hindpaw. For comparison, another

2018 Toxins

55. Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury Full Text available with Trip Pro

Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown.Patterns of MMP-9 expression, activity and excretion were assessed in a model (...) of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI.The

2018 Journal of neuroinflammation

56. Peripheral nerve injury increases contribution of L-type calcium channels to synaptic transmission in spinal lamina II: Role of α2δ–1 subunits Full Text available with Trip Pro

Peripheral nerve injury increases contribution of L-type calcium channels to synaptic transmission in spinal lamina II: Role of α2δ–1 subunits Background Following peripheral nerve chronic constriction injury, the accumulation of the α2δ-1 auxiliary subunit of voltage-gated Ca2+ channels in primary afferent terminals contributes to the onset of neuropathic pain. Overexpression of α2δ-1 in Xenopus oocytes increases the opening properties of Cav1.2 L-type channels and allows Ca2+ influx (...) -sensitive calcium current. In lamina II, gabapentin reduced spontaneous excitatory postsynaptic current frequency in neurons from animals subject to chronic constriction injury but not in those from sham-operated animals. Intraperitoneal injection of 5 mg/kg nitrendipine increased paw withdrawal threshold in animals subject to chronic constriction injury. Conclusion We suggest that L-type channels show an increased contribution to synaptic transmission in lamina II dorsal horn following peripheral nerve

2018 Molecular pain

57. Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries Full Text available with Trip Pro

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory signaling, and motor control; (2) Wallerian rapid (1-3 days) degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months (if ever, after ablations) by slowly (...) dogma and a paradigm shift in clinical treatment of peripheral nerve injuries.

2018 Neural Regeneration Research

58. MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42 Full Text available with Trip Pro

MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42 Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve (...) stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

2018 Molecular pain

59. Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. (Abstract)

Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed (...) -10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats. Finally, in cultured DRG neurons, Cav2.2 was dose-dependently upregulated by IL-1β and downregulated by IL-10. These data indicate that the upregulation of Cav2.2 in uninjured DRG neurons via IL-1β over-production contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.Copyright © 2018 Elsevier Inc. All rights reserved.

2018 Brain, behavior, and immunity

60. Hyperpolarization-activated channels shape temporal patterns of ectopic spontaneous discharge in C-nociceptors after peripheral nerve injury. Full Text available with Trip Pro

Hyperpolarization-activated channels shape temporal patterns of ectopic spontaneous discharge in C-nociceptors after peripheral nerve injury. Neuropathic pain is thought to be mediated by aberrant impulses from sensitized primary afferents, and the temporal summation of the discharges might also influence nociceptive processing. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (Ih current) generate rhythmic activity in neurons within the central nervous system and contribute (...) to nociceptors excitability in neuropathic pain.We searched for single fibres with ectopic spontaneous discharges from an in vitro preparation in mice containing a neuroma formed in a peripheral branch of the saphenous nerve together with the undamaged branches.Both damaged (axotomized) and undamaged fibres (putative intact) developed ectopic spontaneous activity with different temporal spike trains: Clock-like, Irregular or Bursts. The Ih current blocker, ZD7288, significantly suppressed ectopic spontaneous

2018 European Journal of Pain

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