Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured ...peripheral nervous system (PNS) is one of the keys to this system’s remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.
The recurrence rate following the excision of tenosynovial giant cell tumors (TSGCT) of the hand is very high. Intraoperative application of a surgical microscope has been reported. However, to date, ...there are no reports of medium-term outcomes related to this technique. This study aimed to evaluate the medium-term outcomes of tumor excision using surgical microscope for TSGCT of the hand.
A total of 27 patients, who underwent an initial surgery for histologically-confirmed TSGCT of the hand, between 2008 and 2020, were included and evaluated. The mean follow-up time postoperatively was 6.8 years. Tumor recurrence and preoperative tumor characteristics were assessed.
All tumors were adherent to tendons, tendon sheaths, neurovascular structures or periarticular ligaments and capsules. Bony lesions were observed in 11 tumors. The surgical microscope was used in 13 tumors. Recurrences were observed in three tumors (overall recurrence rate: 11%). Tumor characteristics were similar in both groups, but the recurrence rate in the group treated using the surgical microscope was 0%, whereas the recurrence rate in the group treated without the surgical microscope was 21%. Re-operations using the surgical microscope for recurrent tumors were performed, without recurrence postoperatively.
Among patients with TSGCT of the hand treated with tumor excision using the surgical microscope, the postoperative recurrence rate was 0%. Based on the results of this study, the surgical microscope might be used for excision of TSGCTs of the hand.
Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms originating from or differentiating into nerve sheaths of peripheral nerves. Vaginal origin is rare, with only six vaginal primary ...cases reported to date. A 55‐year‐old woman presented to our hospital with a 7 cm vulvar mass. Tumor biopsy results were suspicious of sarcoma, and pelvic magnetic resonance imaging and hysterofiberscopy showed that the tumor originated from the lower vagina. The mass was transvaginally excised, and histological examination confirmed the diagnosis of a vaginal MPNST with negative surgical margins. The patient underwent radiotherapy because the risk of recurrence was high, owing to the large tumor size and high mitotic index. The patient remained recurrence‐free for 1 year after the primary treatment. This is the first case of a high‐risk vaginal MPNST that avoided early disease recurrence with additional radiotherapy after complete tumor resection.
This article reviews the pathology and management of peripheral nerve tumours, including a framework for investigation and decision-making. Most tumours are benign, including schwannomas and ...neurofibromas, but malignant peripheral nerve sheath tumours can occur. The risk of malignant change is remote for schwannomas but higher for neurofibromas, particularly in neurofibromatosis type 1. Magnetic resonance imaging is useful for defining the relationship of a swelling with adjacent nerves but is not definitive for tissue diagnosis. Increasing size, pain and neurological deficit suggest malignant change and TruCut needle biopsy is indicated, although there is a risk of sampling error. Excision biopsy preserving nerve function may be carried out for benign tumours to relieve symptoms. Malignant tumours require a multidisciplinary approach. Complete surgical excision with clear margins is the only curative treatment and may be supplemented with radiotherapy and chemotherapy. However, prognosis remains poor, particularly for patients with neurofibromatosis.
Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked ...whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB-dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-α in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.
To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination associated with chronic hypoxia and ...identified structural and functional deficits of excitatory cortical synapses with a prolonged motor deficit. We demonstrate that genetically delaying myelination phenocopies the synaptic and functional deficits observed in mice after hypoxia, suggesting that myelination may possibly facilitate excitatory presynaptic innervation. As a gain-of-function experiment, we specifically ablated the muscarinic receptor 1 (M1R), a negative regulator of oligodendrocyte differentiation in oligodendrocyte precursor cells. Genetically enhancing oligodendrocyte differentiation and myelination rescued the synaptic loss after chronic hypoxia and promoted functional recovery. As a proof of concept, drug-based myelination therapies also resulted in accelerated differentiation and myelination with functional recovery after chronic hypoxia. Together, our data indicate that myelination-enhancing strategies in preterm infants may represent a promising therapeutic approach for structural/functional recovery after hypoxic WMI.
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•Chronic hypoxia causes hypomyelination, synaptic loss, and functional deficits•Hypomyelination results in synaptic and functional deficits•Enhancing myelination rescues hypoxia-induced synaptic and functional deficits•Myelination-enhancing drugs improve functional recovery against hypoxia
Wang et al. demonstrate that hypomyelination specifically contributes to the significant loss of excitatory synapses and prolonged functional deficits after chronic hypoxia and that myelination-enhancing strategies represent a promising approach for functional recovery following hypoxic WMI.
The performance of aqueous Zn ion batteries (AZIBs) is highly dependent on inner Helmholtz plane (IHP) chemistry. Notorious parasitic reactions containing hydrogen evolution reactions (HER) and Zn ...dendrites both originate from abundant free H2O and random Zn deposition inside active IHP. Here, we report a universal high donor number (DN) additive pyridine (Py) with only 1 vol. % addition (Py‐to‐H2O volume ratio), for regulating molecule distribution inside IHP. Density functional theory (DFT) calculations and molecular dynamics (MD) simulation verify that incorporated Py additive could tailor Zn2+ solvation sheath and exclude H2O molecules from IHP effectively, which is in favor of preventing H2O decomposition. Consequently, even at extreme conditions such as high depth of discharge (DOD) of 80 %, the symmetric cell based on Py additive can sustain approximately 500 h long‐term stability. This efficient strategy with high DN additives furnishes a promising direction for designing novel electrolytes and promoting the practical application of AZIBs, despite inevitably introducing trace organic additives.
The performance of aqueous Zn‐ion batteries is improved by regulating the inner Helmholtz plane (IHP) chemistry. Pyridine (Py) as high donor number organic electrolyte additive (only 1 vol. % addition) is used to efficiently regulate the solvation sheath structure, which results in depressed H2O activity at the IHP interface. The thus‐formed IHP interface enables a superior stable Zn anode with high reversibility and utilization rate.
Metallic Na is a promising anode for rechargeable batteries, however, it is plagued by an unstable solid electrolyte interphase (SEI) and Na dendrites. Herein, a robust anion‐derived SEI is ...constructed on Na anode in a high‐concentration 1,2‐dimethoxyethane (DME) based electrolyte with a cosolvent hydrofluoroether, which effectively restrains Na dendrite growth. The hydrofluoroether can tune the solvation configuration of the electrolyte from three‐dimensional network aggregates to solvent–cation–anion clusters, enabling more anions to enter and reinforce the inner solvation sheath and their stepwise decomposition. The gradient inorganic‐rich SEI leads to a reduced energy barrier of Na+ migration and enhanced interfacial kinetics. These render the Na||Na3V2(PO4)3 battery with an excellent rate capability of 79.9 mAh g−1 at 24 C and a high capacity retention of 94.2 % after 6000 cycles at 2 C. This highlights the modulation of the electrode–electrolyte interphase chemistry for advanced batteries.
A gradient inorganic‐rich interphase is constructed on Na surface in a high‐concentration ether‐based electrolyte with a cosolvent hydrofluoroether. It leads to a configuration of solvent–cation–anion clusters for a reinforced inner solvation sheath. The derived interphase results in a reduced energy barrier for Na+ migration and fast interfacial kinetics, and hence excellent electrochemical performance.
The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of diseases, notably multiple ...sclerosis (MS). In MS, demyelination is associated with progressive axonal damage, which determines the level of patient disability. The few treatments that are available for combating myelin damage in MS and related disorders, which largely comprise anti-inflammatory drugs, only show limited efficacy in subsets of patients. More-effective treatment of myelin disorders will probably be accomplished by early intervention with combinatorial therapies that target inflammation and other processes-for example, signaling pathways that promote remyelination. Indeed, evidence suggests that such pathways might be impaired in pathology and, hence, contribute to the failure of remyelination in such diseases. In this article, we review the molecular basis of signaling pathways that regulate myelination in the CNS and PNS, with a focus on signals that affect differentiation of myelinating glia. We also discuss factors such as extracellular molecules that act as modulators of these pathways. Finally, we consider the few preclinical and clinical trials of agents that augment this signaling.
Malignant Triton Tumors (MTTs) are a rare and aggressive subtype of malignant peripheral nerve sheath tumors (MPNSTs), often associated with neurofibromatosis type 1. This case report describes a ...unique instance of recurrent sporadic MTT within the carotid sheath in a 33-year-old male without any personal or familial history of neurofibromatosis. The patient initially presented with a biopsy-confirmed MTT in the right neck, involving the carotid body and brachial plexus, and underwent partial resection, radiation therapy, and chemotherapy. Six months later, the patient presented with recurrent MTT, and subsequently underwent radical tumor resection, segmental right carotid artery resection, and deep femoral vein interposition. Recovery was complicated by hematoma formation, and the patient developed vocal fold paralysis and a left vocal fold cyst, necessitating further surgeries. Yearly follow-ups for 8 years revealed no recurrence. This case emphasizes the importance of comprehensive patient evaluation, including clinical history, imaging, and biopsy findings, for accurate diagnosis and prompt surgical intervention in managing such rare and aggressive tumors. Further research is needed to identify novel therapies and improve survival rates for patients with MTTs.
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