Macrophages are dispensable for taste bud regeneration upon nerve injury repair.

Vascular cognitive impairment (VCI) is a prevalent and heterogeneous condition, both clinically and pathophysiologically, that still lacks approved treatment. Peripheral electrical nerve stimulation (PENS) shows promise for VCI management, yet its underlying neurobiological mechanisms are not well understood. VCI was induced in rats via permanent bilateral common carotid artery occlusion. Cognitive function was assessed using the Morris water maze, Y-maze, and novel object recognition. Synaptic plasticity was evaluated through long-term potentiation recordings and Golgi staining. The nucleus tractus solitarius (NTS)-medial septum-hippocampus circuit was dissected using fiber photometry recording, immunofluorescence multiplex labeling, in vivo multichannel recordings, anterograde/retrograde tracing, and chemogenetic manipulation. We found that PENS at Zusanli (ST36) acupoint significantly elevated hippocampal acetylcholine levels, enhanced synaptic plasticity, and rescued spatial and nonspatial memory deficits in VCI rats. Chemogenetic activation of cholinergic neurons in the NTS enhanced the cognitive function of VCI rats, whereas chemogenetic inhibition of these neurons counteracted the cognitive benefits of PENS. The NTS sends cholinergic projections to the hippocampal cornu ammonis 1 region through the medial septum. Specific inhibition of NTSChAT-medial septumChAT-cornu ammonis 1 circuit reversed the enhancement of spatial memory observed in VCI rats treated with PENS, while leaving the nonspatial memory unaffected. Our findings identify the NTS-medial septum-cornu ammonis 1 cholinergic circuit as a critical mechanism mediating PENS-induced reversal of spatial memory deficits in VCI, revealing a novel and spatially selective therapeutic target for VCI.

Autologous nerve transplantation is currently recognized as the gold standard for treating severe peripheral nerve injuries in clinical practice. However, challenges such as a limited supply of donors, complications in the donor area, and the formation of neuromas necessitate the optimization of existing transplantation strategies. Additionally, the development of new and promising repair methods is a critical issue in the field of peripheral nerve research. The purpose of this article is to compare the advantages and disadvantages of autologous, allogeneic, decellularized nerve grafts, and cell-composite graft, as well as to summarize the differences in their prognostic factors and associated adverse events. The length, diameter, polarity, and sensory or motor origin of autografts all influence axonal regeneration. While pre-denaturation treatment can accelerate early regeneration, long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts. For decellularized nerve grafts, defect length is identified as an independent risk factor, and the internal microenvironment (delayed angiogenesis, Schwann cell senescence, and reduced T-cell infiltration) is considered a key factor limiting long-segment regeneration. Additionally, the decellularization process (whether chemical, physical, or supercritical CO 2 ) affects the integrity of the extracellular matrix and the presence of immune residuals, which directly impacts axonal guidance and host integration. Common adverse events following autograft transplantation include donor site numbness, neuromas, and scarring. In contrast, adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions, excessive scar proliferation, and misalignment or reconnection of regenerating axons, which can lead to sensory-motor cross-innervation. To mitigate these issues, combining decellularized nerve grafts with autologous Schwann cells, mesenchymal stem cells, or induced pluripotent stem cell-derived cells may help bridge the gap with autografts. However, the fact that structural recovery does not necessarily lead to functional recovery needs further clarification. Future research should establish large animal models to replicate the limits of human regenerative capacity, use gene editing to enhance the phenotype and microenvironment of transplanted cells, and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts. Through multidimensional optimization, decellularized nerve grafts have the potential to ultimately replace autograft transplantation, enabling precise repair of individualized, long-segment, and complex nerve defects.

Peripheral nerve injury (PNI) remains a major regenerative challenge, in part because the post-injury microenvironment can disrupt Schwann cell (SCs) homeostasis. Walnuts (Juglans regia) have long been used in ethnomedicine for perceived neurotrophic or neuroprotective benefits, a view historically linked to their resemblance to the brain. To examine whether this traditional concept can be leveraged as a nanotherapeutic approach, we isolated walnut-derived extracellular vesicles (WEVs) and evaluated their effects on peripheral nerve repair. We found that WEVs are readily internalized by SCs and can help establish a "pre-regenerative niche," defined here as a permissive metabolic microenvironment that supports repair. Mechanistically, WEVs appear to engage a c-Myc-mediated transcriptional program that shifts SC metabolism toward aerobic glycolysis and increases lactate export, consistent with activation of a glia-to-neuron lactate shuttle. In parallel, WEVs may stabilize the glial bioenergetic hub by limiting stress-induced mitophagy. In a rat sciatic nerve compression model, these changes were associated with preserved mitochondrial ultrastructure in the acute phase, followed by enhanced remyelination, improved motor and sensory outcomes, and attenuated muscle atrophy. Collectively, our findings suggest a mechanistic basis for the reported neuroprotective value of walnuts and identify WEVs as a niche-modulating nanotherapeutic candidate that may promote regeneration by aligning glial metabolic plasticity with neuronal energy demands.

Traditional nerve repair methods, such as autologous nerve grafting and allogeneic nerve grafting, face issues such as donor shortage, functional loss, and immune rejection. Decellularized extracellular matrix-based grafts have emerged as highly promising alternatives, capable of uniquely recreating the natural neural microenvironment, promoting host cell remodeling, and ultimately enhancing functional neural regeneration. This review comprehensively analyzes the key mechanisms of peripheral nerve injury and regeneration, focusing on contemporary therapeutic strategies for key aspects such as axonal apoptosis inhibition, enhanced intrinsic regenerative capacity, construction of regenerative microenvironment, and prevention of target organ atrophy. Findings from this review has shown that decellularized extracellular matrix grafts can promote the migration, proliferation, and differentiation of nerve cells by providing physical support, chemical signals, and mechanical stability. Decellularized extracellular matrix grafts are mainly used as nerve conduits, scaffolds, hydrogels, and 3D printing inks. Decellularized extracellular matrix grafts have demonstrated significant advantages in promoting nerve regeneration by regulating the proliferation and differentiation of Schwann cells, improving the neural microenvironment, reducing inflammatory responses, and promoting angiogenesis. Additionally, decellularized extracellular matrix grafts can serve as drug carriers, enabling the controlled release of growth factors, which further enhances nerve regeneration. However, these grafts also have some limitations, including the presence of immunogenic residues, inadequate mechanical properties, inter-batch variability, and uncontrollable degradation rates. Future research should focus on optimizing the decellularization process, enhancing the mechanical properties of decellularized extracellular matrix grafts, reducing immunogenicity, improving biocompatibility and safety, and developing new composite materials. Furthermore, exploring their application potential in complex nerve injuries, such as diabetic neuropathy, is crucial to meet the needs of peripheral nerve regeneration and repair.

Plant-derived extracellular vesicles restore cellular energetics for peripheral nerve regeneration through glycolysis reprogramming.

Sheep models are important in peripheral nerve research due to anatomical similarities to humans. The phrenic nerve, as the sole motor nerve of the diaphragm, represents a crucial structure for understanding peripheral nerve anatomy. This study investigated the gross anatomical characteristics and cervical ventral branch variations of the phrenic nerve in Akkaraman sheep to provide fundamental data for peripheral nerve research. Seven one-year-old male Akkaraman sheep underwent neurological examination. Following euthanasia and perfusion fixation with paraformaldehyde-glutaraldehyde solution, systematic dissection was performed to identify phrenic nerve origins, course and branching patterns. Phrenic nerve formation showed species-specific variations. In four animals (57.1%), the nerve was formed by ventral branches from C5, C6 and C7, whereas in the remaining three animals (42.9%), formation involved ventral branches from C5 and C6 only. Intrathoracic formation occurred in six animals (85.7%) and extrathoracic in one animal (14.3%). Consistent bilateral symmetry of the phrenic nerve was observed in all specimens, accompanied by variations in cervical ventral branch contributions and formation levels. No macroscopically detectable branches supplying the pericardium were identified along the intrathoracic course of the phrenic nerve. These findings support the use of sheep as large animal models for peripheral nerve research and emphasize the need to consider anatomical variability in experimental design.

Peripheral nerve injury increases the probability of thalamocortical burst firing remotely via microglia-dependent enhancement of tonic inhibition.

Chronic pain syndromes represent amajor medical and socioeconomic burden. In both cancer-related and noncancer pain, pharmacological treatment alone is often insufficient or limited by adverse effects, particularly during long-term opioid therapy. Image-guided interventional procedures are therefore increasingly relevant as targeted, opioid-sparing components of multimodal pain management. This narrative review summarizes diagnostic blocks, therapeutic injections, and neurolytic procedures targeting sympathetic plexuses and peripheral nerves. It outlines the principal imaging modalities (computed tomography, fluoroscopy, ultrasound), common indications, and the distinction between diagnostic/prognostic, pharmacological, and definitive neurolytic techniques. Available evidence demonstrates clinically meaningful pain reduction, functional improvement, and opioid-sparing effects in selected indications. The strongest evidence exists for visceral cancer pain, particularly for celiac plexus and splanchnic nerve interventions, and for chronic musculoskeletal pain such as genicular nerve procedures. Image-guided nerve and plexus interventions are effective components of multimodal pain management and can be integrated into interdisciplinary care pathways. Their clinical value depends on careful patient selection, precise anatomical targeting, standardized procedural quality, and structured outcome assessment; they should be considered early rather than only as alast-line option.

The study of nerve-tumor interactions has emerged as a rapidly advancing and interdisciplinary field with profound implications for understanding cancer progression, prognosis, and therapeutic innovation. While this area holds significant promise for transformative discoveries, the mechanisms of nerve-tumor interactions and their translation into clinical applications remain at an early stage. This review focuses on the role of peripheral nerves in non-neurogenic solid tumors, discussing the prevalence and clinical impact of nerve-tumor interactions, their underlying forms and mechanisms, advancements in research technologies, therapeutic potential, and future challenges. By synthesizing current knowledge, integrating methodologies for studying nerve-tumor interactions, and identifying critical gaps, this work aims to provide a foundational resource to guide experimental design and stimulate interest in clinical trials targeting neural influences in cancer progression.

Revisiting Obstetric Brachial Plexus Injuries Through a Central Nervous System Lens: Toward Integrated Diagnostic and Therapeutic Frameworks.

Dexterous hand motor functions are highly flexible and finely controlled by complex neural commands from the motor cortex. However, in patients with brain injuries such as stroke, restoring fine motor control from the perilesional cortex remains extremely challenging. A major obstacle is the absence of appropriate non-human primate models to elucidate the behavioral and neural signatures of hand motor function during recovery following treatments. Here, we present a new non-human primate model that reflects the motor function recovery processes following lesion-induced hand paralysis after contralateral C7 nerve transfer (CC7) surgery, which establishes a new neural pathway from the ipsilateral cortex to control the paralyzed hand. By developing a hand reach-to-pinch task and quantifying finger kinematics, we established systematic, objective profiles of fine motor recovery in human patients and monkey models following CC7 treatment. Furthermore, when considering behavioral aspects, spontaneous recovery of hand motor skills was notably limited in human patients and monkey models, as indicated by the consistently abnormal "thumb-in-palm" patterns observed in finger kinematic analysis. However, the CC7 surgery gradually restored the finger kinematic patterns during hand-pinch actions to nearly identical patterns to those of the healthy hand. In addition, the human functional MRI and macaque electrophysiology results revealed, on a neural level, the emergence of a new command area and its spiking-based motor-command refinements specifically for the paralyzed hand in the contralesional M1 and premotor cortex (PMC) after CC7 treatment. Thus, our findings strongly support the notion that modifying peripheral nerve pathways greatly promotes the recovery of dexterous motor function in a paralyzed hand by reconstructing new motor-control neural mechanisms within the ipsilateral healthy motor cortex.

Evaluation of Peripheral Nerve Blocks for Postoperative Pain Control After Lung Transplantation

Skeletal muscle undergoes progressive denervation-induced muscle atrophy (DIMA) after peripheral nerve injury that severely impairs the potential for motor functional recovery with reinnervation. There are currently no therapeutic strategies to reverse the deleterious effects of chronic DIMA, leaving affected patients with lifelong disability. Herein, we used a translational rodent forelimb nerve injury model to investigate whether targeted injection of syngeneic myoblasts to chronically atrophic muscle can reverse the histologic and functional consequences of DIMA. Male Lewis rats underwent median nerve transection followed by immediate (positive control) or delayed repair. Following a plateau of motor function, myoblasts were injected into the digital flexor muscles (n = 5-6 per group), delivered in either saline or a nanofiber hydrogel composite (NHC) loaded with agrin- and insulin-like growth factor 1 (IGF-1)-releasing nanoparticles (npNHC). Serial functional assessments of stimulated grip strength and terminal histological evaluation were used to measure recovery. Satellite cell-rich (Pax7 Hi ) myoblast therapy caused sustained improvement in stimulated grip strength from pretreatment baseline (p < 0.05). Histological evaluation demonstrated that myoblast therapy, when delivered in npNHC, reversed whole muscle atrophy compared to positive controls [p = 0.997 and 0.996] and restored mean myofiber cross-sectional area [p = 0.244]. Correlation analysis demonstrated functional improvements were associated with increased myofiber cross-sectional area [r = 0.900, p = 3.01E-09]. This data indicates that targeted injection of syngeneic myoblasts can reverse the functional and histologic effects of DIMA in skeletal muscles and is a promising strategy for improving recovery after peripheral nerve injuries.

The study aimed to investigate whether a 5-week sprint interval training (SIT) could improve neuromuscular function (NMF), alter electromyographic activity (EMG), and attenuate fatigability, ultimately resulting in improved cycling performance during constant work rate (CWR) exercise within the severe-intensity domain. Twenty-one recreational active males were randomly assigned into a SIT group (SITG; n=11) that underwent 5weeks of SIT (4-6, 30-s Wingate bouts) and a control group (CON; n=10). The study was conducted in a parallelindependent group study. At the pre- and post-training periods, participants performed (i) a ramp incremental test; (ii) CWR exercise at 150% of the pre- and post-training power output at the respiratory compensation point (RCP-PO) until task failure, with the NMF assessed at baseline (NMFBL) and immediately after exercise [isometric maximal voluntary contraction+peripheral nerve stimulations with measurement of the force and EMG]. Pre- and post-training NMFBL was used to assess isometric performance, whereas the difference between NMFBL and NMF after exercise was used to assess performance fatigability. Furthermore, EMG was also measured during exercise. SITG showed a significant increase in absolute RCP-PO compared to CON (+11.0% vs. -0.7%, respectively; p<0.01), performing the post-training CWR at a greater power output than in pre-training. Despite this, no significative differences were observed for the NMFBL, fatigability, and EMG during CWR exercise. These findings suggest that SIT may improve EMG activity efficiency (i.e.,requiring the same level of activation to sustain a greater absolute power output) during CWR exercise within the severe-intensity domain. However, NMFBL, fatigability, and time-to-task failure performance remained unchanged.

Subdermal contraceptive implants (SCIs) are a widely used form of long-acting reversible contraception (LARC) with high efficacy (Pearl Index 0.00, 95% CI: 0.00-0.14). However, upper limb neurovascular injuries related to SCI insertion and removal are increasingly reported. The true incidence of these complications cannot be reliably estimated from the current literature, which is largely limited to case reports and small case series, although sporadic cases are being described with increasing frequency. These injuries may result in significant morbidity, including chronic neuropathic pain, sensorimotor deficits, and functional impairment, yet standardized management guidelines remain lacking. This study aims to systematically review the literature on SCI-associated upper limb peripheral nerve injuries and present a case series of affected patients treated by the senior authors. The findings are intended to inform evidence-based recommendations for the prevention and management of these injuries. Following PRISMA guidelines, a systematic review of the literature was conducted to identify and characterize SCI-associated PNIs. Data extraction included demographics, injury-related factors (incidence, clinical presentation, implant type, timing of injury (insertion/removal), nerve injury classification and functional deficits at presentation, and treatment-related factors (management strategies and patient outcomes at latest follow-up). A prospectively collated bi-institutional case series of patients presenting with PNI's following SCI procedures is also presented. This systematic review identified 24 patients (mean age 28.5y, range: 19 to 51) with 26 PNIs linked to subdermal contraceptive implants. Most injuries occurred during removal (67%), with the ulnar nerve most frequently affected (52% n=14), followed by the median (26% n=7) and medial antebrachial cutaneous nerves (22% n=6). Injury severity included neuropraxia (33%, n=9), axonotmesis (26%, n=7), axonotmesis with neuroma-in-continuity (33%, n=9), and partial nerve transection (7%, n=2). Surgical intervention was required in 56% (n=13) of cases. At the latest follow-up, 39% (n=9) achieved full recovery, 43% (n=10) had partial recovery, and 9% (n=2) had no recovery. Our case series of 6 patients mirrored these findings, with injuries ranging from transient neuropraxia to persistent deficits. SCI-associated PNIs can cause significant morbidity. The ulnar nerve is particularly at risk, especially during removal, with implant impalpability contributing to injury severity. This study underscores the need for enhanced practitioner training, improved insertion and removal techniques, and consideration of alternative insertion sites to mitigate nerve injury risks. Image-guided removal should be standard practice for impalpable implants.

Peripheral Nerve Blocks as a Primary Anesthetic for Above-the-Knee Amputations: A Prospective Feasibility Study.

Polyneuropathy (PN) in Parkinson's disease (PD) remains underrecognized in clinical practice despite increasing evidence of its prevalence, especially among patients receiving levodopa therapy. Both iatrogenic and neurodegenerative mechanisms have been proposed. This study aimed to assess the prevalence and characteristics of PN in PD patients across different therapeutic regimens, including a longitudinal evaluation of those initiating levodopa-carbidopa intestinal gel (LCIG). We conducted a prospective observational study on 66 PD patients classified into levodopa-naïve (noLEV), moderate-dose (modLEV), and high-dose (highLEV) groups. Clinical, neurophysiological, and biochemical evaluations were performed at baseline. A subgroup of 17 patients initiating LCIG underwent follow-up assessments after a mean of 40 months. PN diagnosis was based on clinical and nerve conduction study (NCS) criteria. At baseline, 22.7% of patients had PN. PN prevalence increased significantly with higher levodopa doses (38.4% in highLEV vs. 10% in noLEV, p = 0.047). Patients with PN had higher homocysteine (Hcy) and lower vitamin B12/folate levels. LEV dosage demonstrated weak positive correlations with Hcy and weak to moderate negative correlations with sensory and motor nerve amplitudes. Among LCIG-treated patients, PN prevalence rose from 17.6% to 47% at follow-up, with a 35.7% incidence of new-onset PN. The change in levodopa dosage was the main predictor of PN development. This study confirms that PN is a common comorbidity in PD, strongly associated with levodopa exposure, particularly at higher doses or via LCIG. Routine clinical, neurophysiological and biochemical monitoring is essential to identify at-risk patients and guide preventive strategies, including vitamin supplementation.

Hyperoside accelerates myelin debris clearance by inhibiting signal transducer and activator of transcription 3 phosphorylation in peripheral nerve injury.

Dexamethasone as an adjuvant to erector spinae plane block is associated with improved neuromonitoring parameters and analgesia in pediatric spine surgery.