Unsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the lesion. In the current study, we subjected rats to complete thoracic (T11) spinal cord transections and examined whether these combinatorial treatments can support dPST axons\' regeneration beyond the transected injury. The results indicated that GDNF significantly improved graft-host interface by promoting integration between SCs and astrocytes, especially the migration of reactive astrocyte into SCs-GDNF territory. The glial response in the caudal graft area has been significantly attenuated. The astrocytes inside the grafted area were morphologically characterized by elongated and slim process and bipolar orientation accompanied by dramatically reduced expression of glial fibrillary acidic protein. Tremendous dPST axons have been found to regenerate across the lesion and back to the caudal spinal cord which were otherwise difficult to see in control groups. The caudal synaptic connections were formed, and regenerated axons were remyelinated. The hindlimb locomotor function has been improved.

Granular cell tumors (GCTs) are neoplasms of uncertain histopathological etiology and therefore there are no universally accepted treatment strategies. GCTs are characterized by abundant eosinophilic granules. Since they are predominantly located in the skin and subcutaneous tissues, gastric GCTs are exceedingly rare. The present study documents the case of a 52-year-old man who visited the Gastroenterology Clinic of the People\'s Hospital of Putuo District (Zhoushan, China) due to upper abdominal fullness. Endoscopic ultrasonography revealed a well-defined hypoechoic nodule in the submucosal layer of the stomach body. The lesion was completely excised using endoscopic submucosal dissection and the patient made a full postoperative recovery. Immunohistochemistry showed positivity for S100 and CD68, with CD34 expression surrounding the tumor cells. At telephone follow-up until May 2024, the patient\'s fullness and discomfort were noted to be relieved. The characteristics of the CD34 expression pattern may serve as a novel basis for the pathological diagnosis of gastric GCTs. Endoscopic resection is a feasible option for gastric GCTs smaller than 2 cm.

BACKGROUND: Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI.
RESULTS: We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation.
CONCLUSIONS: This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.

Schwann cells are found in the peripheral nervous system and can sometimes appear as benign hamartoma lesions in various parts of the body. Although rare in the gastrointestinal (GI) tract, they have been observed in the colon. Recently, mucosal Schwann cell hamartomas of the GI tract have been studied, and it was discovered that they had yet to be investigated up to 2009. In this context, we present the case of a 60-year-old man who was found to have lesions in the transverse colon during a routine colonoscopy. No further investigations were conducted since these lesions have not been associated with any risk of malignancy transformation and have not been linked to any inherited syndromes.
CONCLUSIONS: Mucosal Schwann cell hamartomas are rare types of polyps that can be found anywhere in the gastrointestinal tract.They are benign lesions not usually associated with any inherited syndrome and they are usually found incidentally by endoscopy.These polyps are benign and might not require further follow-up once diagnosed.

OBJECTIVE: The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy.
METHODS: Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21.
RESULTS: In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion.
CONCLUSIONS: Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination.

OBJECTIVE: When operating near cranial motor nerves, transient postoperative weakness of target muscles lasting weeks to months is often observed. As nerves are typically intact at a procedure\'s completion, paresis is hypothesized to result from a combination of neurapraxia and axonotmesis. As both neurapraxia and axonotmesis involve Schwann cell injury and require remyelination, we developed an in vitro RSC96 Schwann cell model of injury using hydrogen peroxide (H2O2) to induce oxidative stress and investigated the efficacy of candidate therapeutic agents to promote RSC96 viability. As a first step in developing a long-term local administration strategy, the most promising of these agents was incorporated into sustained-release microparticles and investigated for bioactivity using this assay.
METHODS: The concentration of H2O2 which reduced viability by 50% was determined to establish a standard for inducing oxidative stress in RSC96 cultures. Fresh cultures were then co-dosed with H2O2 and the potential therapeutics melatonin, N-acetylcysteine, resveratrol, and 4-aminopyridine. Schwann cell viability was evaluated and the most efficacious agent, N-acetylcysteine, was encapsulated into microparticles. Eluted samples of N-acetylcysteine from microparticles was evaluated for retained bioactivity.
RESULTS: 100 µM N-acetylcysteine improved the viability of Schwann cells dosed with H2O2. 100 µM Microparticle-eluted N-acetylcysteine also enhanced Schwann cell viability.
CONCLUSIONS: We developed a Schwann cell culture model of iatrogenic nerve injury and used this to identify N-acetylcysteine as an agent to promote recovery. N-acetylcysteine was packaged into microparticles and demonstrated promise as a locally administrable agent to reduce oxidative stress in Schwann cells.

The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.

Haplo-insufficiency of the gene encoding the myelin protein PMP22 leads to focal myelin overgrowth in the peripheral nervous system and hereditary neuropathy with liability to pressure palsies (HNPP). Conversely, duplication of PMP22 causes Charcot-Marie-Tooth disease type 1A (CMT1A), characterized by hypomyelination of medium to large caliber axons. The molecular mechanisms of abnormal myelin growth regulation by PMP22 have remained obscure. Here, we show in rodent models of HNPP and CMT1A that the PI3K/Akt/mTOR-pathway inhibiting phosphatase PTEN is correlated in abundance with PMP22 in peripheral nerves, without evidence for direct protein interactions. Indeed, treating DRG neuron/Schwann cell co-cultures from HNPP mice with PI3K/Akt/mTOR pathway inhibitors reduced focal hypermyelination. When we treated HNPP mice in vivo with the mTOR inhibitor Rapamycin, motor functions were improved, compound muscle amplitudes were increased and pathological tomacula in sciatic nerves were reduced. In contrast, we found Schwann cell dedifferentiation in CMT1A uncoupled from PI3K/Akt/mTOR, leaving partial PTEN ablation insufficient for disease amelioration. For HNPP, the development of PI3K/Akt/mTOR pathway inhibitors may be considered as the first treatment option for pressure palsies.

UNASSIGNED: Gastric schwannoma is a rare and benign tumor originating from the peripheral nerves of the stomach. Despite its benign nature, this tumor typically remains asymptomatic for an extended period, and its radiological and endoscopic presentation poses challenges in distinguishing it from other gastric mesenchymal tumors.
METHODS: Here, we present a rare case of a patient experiencing gastric pain and melena secondary to a gastric mass. The initial preoperative diagnosis indicated a gastrointestinal stromal tumor, but subsequent pathological and immunohistochemical staining of the surgical specimen confirmed the presence of gastric schwannoma.
CONCLUSIONS: To gain insights into this uncommon condition, we conducted an electronic search on PubMed using the keywords \"gastric schwannoma\" and \"gastric neurinoma.\" Our focus centered on case series containing more than five cases of gastric localization, resulting in the analysis of 14 case series involving a total of 321 patients. Our review aims to comprehensively discuss the clinical, radiological, and therapeutic aspects associated with this rare disease.
CONCLUSIONS: In the absence of a definitive preoperative diagnosis, the surgical approach is considered the primary treatment for resectable gastric schwannoma, given its excellent long-term outcomes. However, further studies are imperative to better define the role of endoscopic resection in managing this condition.

Mutations in myelin protein zero (MPZ) are generally associated with Charcot-Marie-Tooth type 1B (CMT1B) disease, one of the most common forms of demyelinating neuropathy. Pathogenesis of some MPZ mutants, such as S63del and R98C, involves the misfolding and retention of MPZ in the endoplasmic reticulum (ER) of myelinating Schwann cells. To cope with proteotoxic ER-stress, Schwann cells mount an unfolded protein response (UPR) characterized by activation of the PERK, ATF6 and IRE1α/XBP1 pathways. Previous results showed that targeting the PERK UPR pathway mitigates neuropathy in mouse models of CMT1B; however, the contributions of other UPR pathways in disease pathogenesis remains poorly understood. Here, we probe the importance of the IRE1α/XBP1 signalling during normal myelination and in CMT1B. In response to ER stress, IRE1α is activated to stimulate the non-canonical splicing of Xbp1 mRNA to generate spliced Xbp1 (Xbp1s). This results in the increased expression of the adaptive transcription factor XBP1s, which regulates the expression of genes involved in diverse pathways including ER proteostasis. We generated mouse models where Xbp1 is deleted specifically in Schwann cells, preventing XBP1s activation in these cells. We observed that Xbp1 is dispensable for normal developmental myelination, myelin maintenance and remyelination after injury. However, Xbp1 deletion dramatically worsens the hypomyelination and the electrophysiological and locomotor parameters observed in young and adult CMT1B neuropathic animals. RNAseq analysis suggested that XBP1s exerts its adaptive function in CMT1B mouse models in large part via the induction of ER proteostasis genes. Accordingly, the exacerbation of the neuropathy in Xbp1 deficient mice was accompanied by upregulation of ER-stress pathways and of IRE1-mediated RIDD signaling in Schwann cells, suggesting that the activation of XBP1s via IRE1 plays a critical role in limiting mutant protein toxicity and that this toxicity cannot be compensated by other stress responses. Schwann cell specific overexpression of XBP1s partially re-established Schwann cell proteostasis and attenuated CMT1B severity in both the S63del and R98C mouse models. In addition, the selective, pharmacologic activation of IRE1α/XBP1 signaling ameliorated myelination in S63del dorsal root ganglia explants. Collectively, these data show that XBP1 has an essential adaptive role in different models of proteotoxic CMT1B neuropathy and suggest that activation of the IRE1α/XBP1 pathway may represent a therapeutic avenue in CMT1B and possibly for other neuropathies characterized by UPR activation.