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Neuroscience Aug 2023Deferoxamine (DFO) is a potent iron chelator for clinical treatment of various diseases. Recent studies have also shown its potential to promote vascular regeneration...
Deferoxamine (DFO) is a potent iron chelator for clinical treatment of various diseases. Recent studies have also shown its potential to promote vascular regeneration during peripheral nerve regeneration. However, the effect of DFO on the Schwann cell function and axon regeneration remains unclear. In this study, we investigated the effects of different concentrations of DFO on Schwann cell viability, proliferation, migration, expression of key functional genes, and axon regeneration of dorsal root ganglia (DRG) through a series of in vitro experiments. We found that DFO improves Schwann cell viability, proliferation, and migration in the early stages, with an optimal concentration of 25 μM. DFO also upregulates the expression of myelin-related genes and nerve growth-promoting factors in Schwann cells, while inhibiting the expression of Schwann cell dedifferentiation genes. Moreover, the appropriate concentration of DFO promotes axon regeneration in DRG. Our findings demonstrate that DFO, with suitable concentration and duration of action, can positively affect multiple stages of peripheral nerve regeneration, thereby improving the effectiveness of nerve injury repair. This study also enriches the theory of DFO promoting peripheral nerve regeneration and provides a basis for the design of sustained-release DFO nerve grafts.
Topics: Humans; Nerve Regeneration; Ganglia, Spinal; Axons; Deferoxamine; Cells, Cultured; Schwann Cells; Nerve Growth Factors; Peripheral Nerve Injuries
PubMed: 37286159
DOI: 10.1016/j.neuroscience.2023.05.029 -
Muscle & Nerve Jan 2024Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and...
INTRODUCTION/AIMS
Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs.
METHODS
This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years.
RESULTS
A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years.
DISCUSSION
Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.
Topics: Humans; Follow-Up Studies; Retrospective Studies; Peripheral Nervous System Diseases; Adrenal Cortex Hormones; Recurrence; Peripheral Nerves
PubMed: 37936515
DOI: 10.1002/mus.27999 -
Korean Journal of Radiology Nov 2023Magnetic resonance neurography (MRN) is increasingly used to visualize peripheral nerves in vivo. However, the implementation and interpretation of MRN in the brachial... (Review)
Review
Magnetic resonance neurography (MRN) is increasingly used to visualize peripheral nerves in vivo. However, the implementation and interpretation of MRN in the brachial and lumbosacral plexi are challenging because of the anatomical complexity and technical limitations. The purpose of this article was to review the clinical context of MRN, describe advanced magnetic resonance (MR) techniques for plexus imaging, and list the general categories of utility of MRN with pertinent imaging examples. The selection and optimization of MR sequences are centered on the homogeneous suppression of fat and blood vessels while enhancing the visibility of the plexus and its branches. Standard 2D fast spin-echo sequences are essential to assess morphology and signal intensity of nerves. Moreover, nerve-selective 3D isotropic images allow improved visualization of nerves and multiplanar reconstruction along their course. Diffusion-weighted and diffusion-tensor images offer microscopic and functional insights into peripheral nerves. The interpretation of MRN in the brachial and lumbosacral plexi should be based on a thorough understanding of their anatomy and pathophysiology. Anatomical landmarks assist in identifying brachial and lumbosacral plexus components of interest. Thus, understanding the varying patterns of nerve abnormalities facilitates the interpretation of aberrant findings.
Topics: Humans; Magnetic Resonance Imaging; Imaging, Three-Dimensional; Lumbosacral Plexus; Magnetic Resonance Spectroscopy
PubMed: 37899521
DOI: 10.3348/kjr.2023.0150 -
Anatomical Science International Sep 2023Traumatic axonal damage disrupts connections between neurons, leading to the loss of motor and sensory functions. Although damaged peripheral nerves can regenerate,...
Traumatic axonal damage disrupts connections between neurons, leading to the loss of motor and sensory functions. Although damaged peripheral nerves can regenerate, recovery depends on the variety and severity of nerve damage. Thus, many phytochemicals have been studied for their ability to reduce peripheral nerve degeneration, and among them, Parthenolide (PTL), which is extracted from Feverfew has effects against production of free radicals, inflammation, and apoptosis. Thus, we conducted a study to investigate whether PTL has an inhibitory effect on peripheral nerve degeneration during peripheral nerve damage. To verify the effect of PTL on peripheral nerve degeneration process, a morphological comparison of peripheral nerves with and without PTL was performed. PTL significantly reduced the quantity of fragmented ovoid formations at 3DIV (days in vitro). Immunostaining for MBP revealed that the ratio of intact myelin sheaths increased significantly in sciatic nerve with PTL compared with absence of PTL at 3DIV. Furthermore, nerve fibers in the presence of PTL maintained the continuity of Neurofilament (NF) compared to those without at 3DIV. Immunostaining for LAMP1 and p75 NTR showed that the expression of LAMP1 and p75 NTR decreased in the nerve after PTL addition at 3DIV. Lastly, immunostaining for anti-Ki67 revealed that PTL inhibited Ki67 expression at 3DIV compared to without PTL. These results confirm that PTL inhibits peripheral nerve degenerative processes. PTL may be a good applicant to inhibit peripheral nerve degeneration. Our study examined the effect of Parthenolide in preventing degeneration of peripheral nerves by inhibiting the breakdown of peripheral axons and myelin, also inhibiting Schwann cell trans-dedifferentiation and proliferation.
Topics: Humans; Axons; Schwann Cells; Sesquiterpenes; Nerve Degeneration; Sciatic Nerve; Peripheral Nervous System Diseases; Nerve Regeneration
PubMed: 37024641
DOI: 10.1007/s12565-023-00718-6 -
Neurosurgery Dec 2023Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new...
BACKGROUND AND OBJECTIVES
Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA).
METHODS
A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses.
RESULTS
The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA.
CONCLUSION
The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.
Topics: Sheep; Animals; Peripheral Nerve Injuries; Peroneal Nerve; Schwann Cells; Transplantation, Autologous; Muscle, Skeletal; Nerve Regeneration; Sciatic Nerve; Peripheral Nerves
PubMed: 37319401
DOI: 10.1227/neu.0000000000002572 -
Der Nervenarzt Dec 2023The functional deficits that develop after a peripheral nerve injury mean a considerable reduction in the quality of life for the affected patients. However,... (Review)
Review
BACKGROUND
The functional deficits that develop after a peripheral nerve injury mean a considerable reduction in the quality of life for the affected patients. However, interventions on the injured nerve are not always possible or effective. In this case, secondary procedures, e.g. tendon transfers, are a feasible option for functional reconstruction.
OBJECTIVES
An overview of the most common secondary surgical procedures for functional reconstruction after peripheral nerve injuries.
METHODS
Presentation and discussion of the most common secondary surgical procedures with emphasis on tendon transfers. Illustration of the primary functions that need to be reconstructed depending on the respective nerve lesion.
RESULTS
The basic principle of secondary surgical procedures after nerve injuries is the transposition of a healthy tendomuscular unit to replace a lost function following a loss of muscle or tendon or if an intervention on the nerve is not promising. For example, by transferring flexor forearm muscles, wrist, finger and thumb extension can be reconstructed after radial nerve injury. By transposing the tibialis posterior muscle, dorsiflexion in the talocrural joint can be restored to enable the affected patient to walk safely without an orthosis.
CONCLUSIONS
Secondary surgical procedures are a valuable option for functional reconstruction after nerve injury.
Topics: Humans; Quality of Life; Radial Nerve; Peripheral Nervous System Diseases; Fingers; Tendon Transfer
PubMed: 37721574
DOI: 10.1007/s00115-023-01543-y -
Journal of Neurosurgery Nov 2023Intrinsic function is indispensable for dexterous hand movements. Distal ulnar nerve defects can result in intrinsic muscle dysfunction and sensory deficits. Although...
OBJECTIVE
Intrinsic function is indispensable for dexterous hand movements. Distal ulnar nerve defects can result in intrinsic muscle dysfunction and sensory deficits. Although the ulnar nerve's fascicular anatomy has been extensively studied, quantitative and topographic data on motor axons traveling within this nerve remain elusive.
METHODS
The ulnar nerves of 14 heart-beating organ donors were evaluated. The motor branches to the flexor carpi ulnaris (FCU) and flexor digitorum profundus (FDP) muscles and the dorsal branch (DoBUN) as well as 3 segments of the ulnar nerve were harvested in 2-cm increments. Samples were subjected to double immunofluorescence staining using antibodies against choline acetyltransferase and neurofilament.
RESULTS
Samples revealed more than 25,000 axons in the ulnar nerve at the forearm level, with a motor axon proportion of only 5%. The superficial and DoBUN showed high axon numbers of more than 21,000 and 9300, respectively. The axonal mapping of more than 1300 motor axons revealed an increasing motor/sensory ratio from the proximal ulnar nerve (1:20) to the deep branch of the ulnar nerve (1:7). The motor branches (FDP and FCU) showed that sensory axons outnumber motor axons by a ratio of 10:1.
CONCLUSIONS
Knowledge of the detailed axonal architecture of the motor and sensory components of the human ulnar nerve is of the utmost importance for surgeons considering fascicular grafting or nerve transfer surgery. The low number of efferent axons in motor branches of the ulnar nerve and their distinct topographical distribution along the distal course of the nerve is indispensable information for modern nerve surgery.
Topics: Humans; Ulnar Nerve; Forearm; Muscle, Skeletal; Elbow; Axons; Nerve Transfer
PubMed: 37029679
DOI: 10.3171/2023.2.JNS23180 -
BMJ Supportive & Palliative Care Dec 2023Patients with cancer often suffer severe pain that is not relieved with systemic analgesics and requires further treatment options. This study aims to investigate...
OBJECTIVES
Patients with cancer often suffer severe pain that is not relieved with systemic analgesics and requires further treatment options. This study aims to investigate whether peripheral nerve blocks are a feasible treatment option in patients with incurable cancer who suffer from severe pain.
METHODS
All patients with advanced cancer who received a peripheral nerve block for the management of pain at the Tampere University Hospital between January 2015 and December 2018 were included in this retrospective study. The characteristics of the patients' features of the nerve blocks, opioid dosing (daily morphine equivalent) before and after the blocks, and patient-reported pain relief following peripheral block were assessed from the medical records.
RESULTS
Sixteen of the 17 patients included in this study received pain relief through a nerve block. Daily opioid dose was decreased with the block in 12 (71%) patients with a median change in daily morphine equivalent of -20 mg (IQR: -180 to 9). One infection of the catheter and two other transient adverse events occurred, but none was serious or fatal.
CONCLUSIONS
Peripheral nerve blocks seem safe and may provide considerable analgesia and decrease the need for opioids in patients with advanced cancer.
Topics: Humans; Retrospective Studies; Analgesics, Opioid; Cancer Pain; Pain, Postoperative; Peripheral Nerves; Morphine; Neoplasms
PubMed: 34857538
DOI: 10.1136/bmjspcare-2021-003293 -
European Journal of Neurology Apr 2024There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of...
Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.
BACKGROUND AND PURPOSE
There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated.
METHODS
We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP.
RESULTS
According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did.
CONCLUSIONS
The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Peripheral Nerves; Neural Conduction; Databases, Factual
PubMed: 38165011
DOI: 10.1111/ene.16190 -
The Journal of Biological Chemistry Dec 2023Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and...
Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.
Topics: Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Animals; Rats; Rats, Sprague-Dawley
PubMed: 37949219
DOI: 10.1016/j.jbc.2023.105444