Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends DOI Creative Commons
Drifa Frostadottir, Charlotte Welinder,

Raquel Perez

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: July 2, 2024

Introduction Proteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate molecular patterns underlying a digital injury, differences protein expression between ends. Methods A total 26 samples (24 men; 2 women; median age 47 [30–66] years), harvested during primary repair within 48 h post-injury from were analyzed using mass spectrometry. Results 3,914 proteins identified, with 127 showing significant abundance The downregulation end was associated synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion migration. Conversely, upregulated implicated cellular stress response, neuromuscular junction stability muscle contraction, neuronal excitability release, vesicle recycling axon guidance angiogenesis. Discussion Investigation proteins, functional annotations analysis, ends revealed dynamic responses at promoting tissue degeneration restoration, while suppressing non-essential processes.

Language: Английский

Carpal tunnel syndrome DOI
Lars B. Dahlin, Malin Zimmerman, Maurizio Calcagni

et al.

Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 23, 2024

Language: Английский

Citations

16

Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations DOI Creative Commons
Christina Brock, Henning Andersen,

Amra Ciric Alibegovic

et al.

Diabetes Research and Clinical Practice, Journal Year: 2025, Volume and Issue: unknown, P. 112010 - 112010

Published: Jan. 1, 2025

Diabetic neuropathy (DN) affects up to half of individuals with type 1 and 2 diabetes. Despite evidence that improving metabolic cardiovascular health can slow its progression, DN remains a significant clinical challenge due the lack disease-modifying therapies effective pain management strategies. This consensus aimed identify gaps recommend strategies address these challenges. A workshop, initiated by Steno Diabetes Centre Copenhagen Danish Endocrinology Academy, conducted gap analysis based on insights from studies, observational cohorts, practice. Online invitations targeted experienced clinicians, researchers, drug developers committed treatment through innovative trials. Thirty-five participants six countries reached via Delphi process key steps advance therapy. Four critical barriers needs were addressed: (1) Translating bench research practice, (2) Enhancing trial design, (3) Improving outcome measures, (4) Identifying treatments for painful DN. Successful interventional trials require robust measures capture clinically meaningful changes in phenotypes, providing basis developing effective, treatments.

Language: Английский

Citations

0

Refinement of Protein Extraction Protocols for Human Peripheral Nerve Tissue DOI Creative Commons
Drifa Frostadottir, Charlotte Welinder,

Raquel Perez

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(5), P. 5111 - 5118

Published: Feb. 2, 2025

Our aim was to establish an effective method for protein extraction from freshly frozen human peripheral nerves, determine the minimum amount required consistent outcomes, and assess which produced highest number of identities. Five methods were compared using 8 M urea Ripa buffer either Bullet Blender or Bioruptor. Out total 2619 identified proteins, combined with Bioruptor resulted in identification 1582 (60%) 1615 (62%) respectively. In contrast, 1022 proteins (39%), whereas employing yielded 1446 (55%). Sample amounts, ranging 0.6 10 mg, prepared outcome obtained samples ≥1.2 mg. Combining increased 2126 (81%). Proteins classified by their cell components, molecular functions, biological processes. Furthermore, a subclassification involved extracellular matrix (ECM) introduced. We recommend use buffer, combination extracting fresh-frozen nerves weighing

Language: Английский

Citations

0

Lactoferrin-derived peptide PXL01 impacts nerve regeneration after sciatic nerve reconstruction in healthy and diabetic rats DOI Creative Commons
Derya Burcu Hazer, Margit Mahlapuu,

Raquel Perez

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 7, 2025

Although advanced surgical techniques are available, satisfactory functional outcomes after peripheral nerve injuries uncommon. Hence, immune-modulating factors such as PXL01, a lactoferrin-derived peptide that improves axonal outgrowth in injured human digital nerves, have gained attention. We previously reported short-term immunosuppressive effect of PXL01 the repair transected rat sciatic but it had no on regeneration. Here, we investigated potential to improve regeneration healthy rats and model type 2 diabetes (Goto-Kakizaki [GK] rats). A 10-mm defect was created (n = 14) diabetic GK reconstructed using autografts. Immediately surgery, or sodium chloride (control, placebo) 7 for each treatment) administered around autograft. On day 8, immunohistochemical staining dorsal root ganglia (DRGs) performed analyze (neurofilament staining); inflammation (CD68 CD206 macrophage nerve); Schwann cell sensory neuron activation (transcription factor ATF3 DRGs) apoptosis (cleaved caspase 3 neuroprotection (heat shock protein [HSP27] DRGs). impact response autografts increased HSP27 expression DRGs rats, despite lower number activated cells Diabetes affected outgrowth, responses, expression. These effects were observed well DRG. Application having macrophages, may affects autograft-reconstructed conveys (HSP27 expression) rats. influenced Therefore, is promising candidate

Language: Английский

Citations

0

DA.Vra1-congenic rats display increased gene expression and Schwann cell apoptosis but unaffected nerve regeneration compared to parental DA rats after sciatic nerve injury and repair DOI Creative Commons
Lena Stenberg,

Michael Jewett,

Alfredo Dueñas Rey

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 28, 2025

The rat Vra1 locus, containing glutathione S-transferase alpha 4 (Gsta4), regulates the degeneration of central nervous system (CNS) neurons in toxin-, protein-, and injury-based models. We hypothesize that Piebald Virol Glaxo.1AV1 (PVG) alleles confer protection increased axonal outgrowth after peripheral nerve injury repair. DA rats (n = 14) with PVG locus (DA.Vra1, n were subjected to sciatic transection immediate After 6 days, protein gene expression analyzed injured uninjured nerves dorsal root ganglia (DRG). No differences observed between strains, but number apoptotic Schwann cells distal end was higher DA.Vra1 than (p 0.003). In both gene- activating transcription factor 3 (ATF3) 27-kDa heat shock (HSP27, i.e., Hspb1) vs. DRG. rats, Gsta4 lower DRG 0.043) 0.008) 0.008). had Atf3 0.016) caspase 0.032) rats. Results highlight complexity repair, supporting further investigation regeneration.

Language: Английский

Citations

0

Serum levels of biomarkers related to severity staging of Raynaud’s phenomenon, neurosensory manifestations, and vibration exposure in patients with hand-arm vibration injury DOI Creative Commons
Eva Tekavec, Tohr Nilsson, Lars B. Dahlin

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 5, 2024

Abstract Our aim was to explore possible relationships between serum levels of biomarkers in patients with hand-arm vibration injury relation the severity vascular, i.e., Raynaud’s phenomenon (RP), and neurosensory manifestations, current exposure level, duration exposure. This study case series design involved 92 diagnosed injury. Jonckheere’s trend test used assess any association RP as well graded by International Consensus Criteria. Generalized linear models adjustment for confounders were also associations and; (1) recorded extent finger blanching calculated Griffin score, (2) perception thresholds, (3) magnitude [A(8); (m/s 2 )] value, (4) years. Serum thrombomodulin, von Willebrand factor, calcitonin gene related peptide (CGRP), heat shock protein 27, caspase-3 positively associated RP. CGRP component. No shown these . For Intercellular adhesion molecule 1 monocyte chemoattractant 1, no found neither nor Levels endothelial or dysfunction, inflammation, vasodilation, neuroprotection, apoptosis

Language: Английский

Citations

3

Autophagy-targeting modulation to promote peripheral nerve regeneration DOI Creative Commons
Yan Chen, Hongxia Deng, Nannan Zhang

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(7), P. 1864 - 1882

Published: May 10, 2024

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors intricate molecular mechanisms. Past studies have focused on that stimulate axonal outgrowth myelin regeneration. However, recent highlighted the pivotal role of autophagy in regeneration, particularly context injuries. Consequently, autophagy-targeting modulation has emerged as promising therapeutic approach to enhancing Our current understanding suggests activating facilitates rapid clearance damaged axons sheaths, thereby neuronal survival mitigating injury-induced oxidative stress inflammation. These actions collectively contribute creating favorable microenvironment for structural functional A range autophagy-inducing drugs interventions demonstrated beneficial effects alleviating neuropathy promoting preclinical models This review delves into regulation cell types involved summarizing potential can be harnessed promote this process. We hope our will offer novel insights perspectives exploitation pathways treatment neuropathies.

Language: Английский

Citations

2

Elucidation of the role of microglia‐macrophage‐based neuroinflammation in neurological diseases DOI Creative Commons
Ryo Yamasaki

Neurology and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: 12(6), P. 329 - 339

Published: May 22, 2024

Abstract Objective To elucidate the roles of microglia and macrophages in neuroinflammation their dual impact on progression neurological diseases. Background Microglia are integral components central peripheral nervous systems, where they play important maintaining homeostasis, influencing disease progression, facilitating repair mechanisms. Methods The review integrates recent advancements single‐cell RNA sequencing that highlight extensive heterogeneity macrophages, which helps understanding wide‐ranging different conditions. Results analysis reveals have a nature, capable both exacerbating mitigating processes across various conditions, including Alzheimer’s disease, multiple sclerosis, stroke, nerve disorders, brain tumors. Conclusion Modulating activity offers promising avenue for therapeutic interventions disorders. There is critical need further research to fully leverage potential targeting enhance patient outcomes.

Language: Английский

Citations

2

PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats DOI
Derya Burcu Hazer, Lena Stenberg, Margit Mahlapuu

et al.

Regenerative Medicine, Journal Year: 2024, Volume and Issue: 19(6), P. 327 - 343

Published: June 2, 2024

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated regeneration processes of PXL01 – a lactoferrin-derived peptide after repair the sciatic in healthy Wistar rats. Materials & methods: PXL01, sodium hyaluronate (carrier) or chloride was administered around repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages nerve, sensory neuronal response dorsal root ganglia (DRG) expression heat shock protein 27 (HSP27) nerves DRGs were analyzed. Results: Despite lower number pan-macrophages, other variables did not differ between groups. Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages repaired without any impact on macrophages.

Language: Английский

Citations

2

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends DOI Creative Commons
Drifa Frostadottir, Charlotte Welinder,

Raquel Perez

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: July 2, 2024

Introduction Proteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate molecular patterns underlying a digital injury, differences protein expression between ends. Methods A total 26 samples (24 men; 2 women; median age 47 [30–66] years), harvested during primary repair within 48 h post-injury from were analyzed using mass spectrometry. Results 3,914 proteins identified, with 127 showing significant abundance The downregulation end was associated synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion migration. Conversely, upregulated implicated cellular stress response, neuromuscular junction stability muscle contraction, neuronal excitability release, vesicle recycling axon guidance angiogenesis. Discussion Investigation proteins, functional annotations analysis, ends revealed dynamic responses at promoting tissue degeneration restoration, while suppressing non-essential processes.

Language: Английский

Citations

0