Peripheral Nerve Injury Research Articles

The effect of 807-nm light-emitting diode photobiomodulation on peripheral nerve injury.

Photobiomodulation (PBM) has demonstrated potential in promoting peripheral nerve regeneration. However, there is a limited and inconclusive study on the application of light-emitting diode (LED) for nerve injury repair. In this study, we designed an 807-nm LED device with high luminous uniformity to investigate the effects of LED-based PBM on peripheral nerve injury repair. RSC96 cells were utilized as the target cells and optimal light parameters were selected based on ATP concentration, CCK-8 assays, PCR, and immunofluorescent staining. One-way analysis of variance and Student's t-test was used for statistical tests. LED irradiation at 10 mW/cm2 for 30 min effectively enhanced Schwann cell proliferation, neurotrophic factor secretion, and MBP synthesis. To translate the cellular light parameters for animal studies, the transmittance through freshly obtained rat skin and biceps femoris muscle was assessed, and the transmittance was approximately 30%. After directly daily irradiating the sciatic nerve injury area in rats for 21 days at 33 mW/cm2 for 30 min, we used gait analysis, immunofluorescence staining, muscle wet weight ratio, Masson staining, and transmission electron microscopy to evaluate nerve recovery. LED irradiation significantly improved sciatic nerve index, increased MBP staining intensity, and enhanced myelin sheath thickness, nerve diameter, and axon diameter. These results indicated the feasibility of LED-based PBM as a treatment method for peripheral nerve injuries.

Bridging the Gap: Contemporary Paradigms in Nerve Scaffolds and Regeneration.

Peripheral nerve injuries, especially those with complete transection of major nerves, create significant morbidity including debilitating pain, loss of protective haptic feedback, and impaired volitional control of musculature. The societal burden and cost of medical care for these injuries are enormous, with estimates in the United States alone in excess of $670 million per year. In clinical scenarios with a segmental nerve gap where end-to-end coaptation without tension is not possible, a "bridge" or scaffold must be interposed to facilitate communication between the proximal and distal stumps to facilitate organized growth following Wallerian degeneration. A multitude of constructs have been created and studied to facilitate this regeneration. Among the three overall types of bridge employed in contemporary clinical care-conduit/scaffold, allograft, and autograft-each has significant downsides ranging from limited successful nerve ingrowth to donor site morbidity. Despite the tremendous work over the last 150 years in nerve biology and medical technology for the treatment of peripheral nerve injury, the biological processes governing nerve regeneration remain incompletely understood. Especially in cases of long segmental gaps, there remains room for significant improvement. Ongoing studies have identified several promising modalities for nerve scaffolds to facilitate more efficient and effective neuronal outgrowth but still require further investigation. Here, we review contemporary paradigms in the treatment of segmental nerve injuries with interposing scaffolds and reexamine nerve physiology, regulatory programs in nerve regeneration, and strategic targets for neurogenic pathways that may facilitate novel treatment modalities.

A glutamatergic innervation from medial area of secondary visual cortex to lateral posterior thalamic nucleus facilitates nociceptive and neuropathic pain

Neuropathic pain involves complex cortical mechanisms, yet the role of the medial secondary visual cortex (V2M) remains poorly understood. We hypothesized that glutamatergic neurons in V2M (V2MGlu) contribute to pain modulation and explored their functional involvement in both normal and neuropathic pain states. Here, we found that V2MGlu could be activated by peripheral stimulation under normal conditions. Optical inhibition or activation of unilateral V2MGlu respectively decreased or increased bilateral nociceptive sensitivity, with activation also inducing aversive emotions. Tracing experiments revealed that V2MGlu sends dense synaptic projections to the lateral posterior thalamic nucleus (LP) and lateral dorsal thalamic nucleus (LD). Notably, only optical manipulation of V2MGlu terminals in LP, rather than LD, affected bilateral pain perception. Following partial sciatic nerve ligation (PSL), V2MGlu exhibited hyperactivity, including increased spontaneous spike frequency and heightened responses to stimulation. Inhibiting V2MGlu alleviated PSL-induced mechanical allodynia, thermal hyperalgesia, and negative affective states related to pain. Inhibition of V2MGlu terminals in LP mitigated neuropathic pain. Here, we identified V2MGlu and its circuits to LP as part of the endogenous pain modulatory network, hyperactive after peripheral nerve injury and contributing to neuropathic pain. Our findings support targeting V2MGlu and related circuits as potential therapeutic strategies for neuropathic pain.

Investigating the Mechanism of Conditioning Versus Postoperative Electrical Stimulation to Enhance Nerve Regeneration: One Therapy, Two Distinct Effects.

Regeneration after peripheral nerve injury is often insufficient for functional recovery. Postoperative electrical stimulation (PES) following injury and repair significantly improves clinical outcomes; recently, conditioning electrical stimulation (CES), delivered before nerve injury, has been introduced as a candidate for clinical translation. PES accelerates the crossing of regenerating axons across the injury site, whereas CES accelerates the intrinsic rate of axonal regeneration; thus, it is likely that their mechanisms are distinct. The large body of literature investigating the mechanisms of electrical stimulation has not differentiated between CES and PES. In this review, we investigate the CES and PES paradigms within the existing literature, distinguish their mechanistic insights, and identify gaps in the literature. A systematic literature review was conducted, selecting articles identifying the pro-regenerative effects of electrical stimulation in the setting of peripheral nerve injury. As a mechanistic template, both paradigms implicate cation channels for the initiation of numerous signaling pathways that together upregulate regeneration-associated genes. CES and PES feature some overlap; activation of PI3K and MAPK signaling pathways, and upregulation of BDNF, GAP43, and GFAP are similar. Currently, the inflammatory environment in which PES is administered predominantly differentiates these mechanisms. However, gaps within the literature complicate the comparison between paradigms. Systematic review revealed the mechanisms for both CES and PES paradigms remain fragmented; though much of the literature assumes the involvement of particular signaling pathways, the evidence remains limited. Though it is likely there is overlap between mechanisms, further investigation is needed.

Targeted Polymersomes Enable Enhanced Delivery to Peripheral Nerves Post-Injury.

The gold standard therapy for peripheral nerve injuries involves surgical repair, which is invasive and leads to major variations in therapeutic outcomes. Because of this, smaller injuries often go untreated. However, alternative, noninvasive routes of administration are currently unviable due to the presence of the blood-nerve barrier (BNB), which prevents passage of small molecules from the blood into the endoneurium and the nerve. This paper demonstrates that ligands on the surface of nanoparticles, called polymersomes, can enable delivery to the nerve through noninvasive intramuscular injections. Polymersomes made from polyethylene glycol (PEG)-b-polylactic acid (PLA) were conjugated with either apolipoprotein E (ApoE) or rabies virus glycoprotein-based peptide RVG29 (RVG) and loaded with near-infrared dye, AlexaFluor647. ApoE was used to target receptors upregulated in post-injury inflammation, while RVG targets neural-specific receptors. Untagged, ApoE-tagged, and RVG-tagged polymersomes were injected at 100 mM either intranerve (IN) or intramuscular (IM) into Sprague-Dawley rats post sciatic nerve injury. The addition of the ApoE and RVG tags enabled increased AlexaFluor647 fluorescence in the injury site at 1 h post IN injection compared to the untagged polymersome control. However, only the RVG-tagged polymersomes increased the AlexaFluor647 fluorescence after IM injection. Ex vivo analysis of sciatic nerves demonstrated that ApoE-tagged polymersomes enabled the greatest retention of AlexaFluor647 regardless of the injection route. This led us to conclude that using ApoE to target inflammation enabled the greatest retention of polymersome-delivered payloads while using RVG to target neural cells more specifically enabled the penetration of polymersome-delivered payloads. Observations were confirmed by calculating the area under the curve pharmacokinetic parameters and the use of a two-compartment pharmacokinetic model.

THE CHOICE OF SURGICAL TACTICS FOR THE TREATMENT OF PERIPHERAL NERVES IN COMBAT TRAUMA

Peripheral nerve injuries are a common complication of bullet, highexplosive and mine blast wounds of the upper and lower extremities. Understanding the multifactorial spectrum of pathogenetic mechanisms of nerve fiber damage and choosing the appropriate time parameters for providing the necessary surgical care are necessary for specialized treatment of this complex traumatic process. The article discusses the pathophysiological factors of traumatic damage to peripheral nerves, presents the most appropriate classification of injuries and wounds of the peripheral nervous system, the preferred timing of surgical intervention. Considering that severe trauma of peripheral nerves leads to loss of ability to work and frequent disability of military personnel, it is necessary to know the pathophysiological factors that influence the choice of timely and adequate surgical care for a fast recovery and to prevent the complications.

Transient receptor potential vanilloid-1 (TRPV1) is a mediator of noise-induced neural damage in zebrafish and mice.

Sound pollution (noise) is an increasing environmental concern, particularly associated with neurological and neurobehavioral abnormalities. However, the molecular mechanisms underlying noise-induced neural damage remain unclear. In this study, we conducted transcriptional profiling of zebrafish to investigate the mechanisms underlying acoustic stimulation (1,000 Hz, 130 dB). RNA sequencing and subsequent experiments revealed that TRPV1 is an important mediator of noise-induced neural damage in HuC(elavl3)-GFP transgenic zebrafish. The results demonstrated that inhibiting TRPV1 significantly mitigated noise-induced neural damage in zebrafish with trpv1 gene RNAi and in mice with Trpv1 knockout (Trpv1-/-). Specifically, TRPV1 antagonism significantly reduced neural damage in zebrafish and mice under noise exposure. Furthermore, activated TRPV1 could induce endoplasmic reticulum stress, leading to apoptosis and resulting in neural damage in mice and HEK293T cells. The findings of this study not only enhance our understanding of the molecular mechanisms underlying sound-induced neural damage but also highlight a novel target for drug intervention.

Akkermansia muciniphila Akk11 Supplementation Attenuates MPTP-Induced Neurodegeneration by Inhibiting Microglial NLRP3 Inflammasome.

The gut dysbiosis is associated with the progression of Parkinson's disease (PD). Probiotics have been demonstrated to impact disease progression via the gut-brain axis. This study aims to investigate the therapeutic potential of Akkermansia Muciniphila Akk11(Akk11) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Our results indicated that Akk11 administration significantly improved the MPTP-induced behavioral abnormalities, reduced the loss of dopaminergic neurons, microglia activation, reversed the production of inflammatory cytokines, and colonic damage. Mechanistic studies showed that Akk11 administration suppressed inflammatory responses by inhibiting microglial NLRP3 inflammasome activation. In summary, Akk11 alleviated MPTP-induced motor deficits and neural damage by inhibiting microglial NLRP3 inflammasome. These findings suggest that Akk11 supplementation has therapeutic potential in treating PD through the gut-brain axis.

The Role of Sensory Impairments on Recovery and Rehabilitation After Stroke.

The current review aims to address critical gaps in the field of stroke rehabilitation related to sensory impairment. Here, we examine the role and importance of sensation throughout recovery of neural injury, potential clinical and experimental approaches for improving sensory function, and mechanism-based theories that may facilitate the design of sensory-based approaches for the rehabilitation of somatosensation. Recently, the field of neurorehabilitation has shifted to using more quantitative and sensitive measures to more accurately capture sensory function in stroke and other neurological populations. These approaches have laid the groundwork for understanding how sensory impairments impact overall function after stroke. However, there is less consensus on which interventions are effective for remediating sensory function, with approaches that vary from clinical re-training, robotics, and sensory stimulation interventions. Current evidence has found that sensory and motor systems are interdependent, but commonly have independent recovery trajectories after stroke. Therefore, it is imperative to assess somatosensory function in order to guide rehabilitation outcomes and trajectory. Overall, considerable work in the field still remains, as there is limited evidence for purported mechanisms of sensory recovery, promising early-stage work that focuses on sensory training, and a considerable evidence-practice gap related to clinical sensory rehabilitation.

Hemodialysis treatment high-dose quetiapine fumarate poisoning: A case report

Introduction: Quetiapine is a new atypical antipsychotic with minor side effects. There have been few reports of rhabdomyolysis and acute kidney injury associated with quetiapine overdose. Case Presentation: This article presents a rare case of high-dose quetiapine poisoning that improved after treatment. The patient experienced rhabdomyolysis, acute kidney injury, long QT syndrome, and peripheral nerve injury, all of which are typical complications of quetiapine poisoning. Moreover, a kidney biopsy verified the patient’s acute tubulointerstitial injury, and immunohistochemical staining demonstrated that myoglobin cast nephropathy was the cause of the injury. This patient’s kidney function and associated complications recovered after receiving hemodialysis, rehabilitation, heart rate regulation, and further symptomatic interventions. Consequently, hemodialysis was discontinued. Conclusion: Our case showed that myoglobin cast nephropathy was the cause of the acute kidney injury associated with quetiapine poisoning. The kidney biopsy is essential for accurate diagnosis and treatment.

Biofabrication of tri-layered nerve guide conduits for peripheral nerve regeneration: Synergizing melt-electrowriting of polymeric fibers and extrusion-based 3D bioprinting

Nerve guide conduits (NGCs) are promising alternatives to autografts for the treatment of peripheral nerve injuries. These conduits are designed to replace the nerve tissue that has been damaged or removed from the injured nerve region. An ideal nerve conduit should effectively bridge the nerve gap and induce nerve cell growth and regeneration. Current FDA-approved NGCs predominantly address gaps smaller than 2 cm and are fabricated from rigid synthetic polymers. Nevertheless, cells prefer softer substrates that more closely mimic the extracellular matrix (ECM). While hydrogels emerge as an ideal ECM-mimicking material, their application is limited by challenges in suturing, maintaining structural integrity, and susceptibility to rapid biodegradation. In this study, we propose a tri-layered NGC biofabricated by combining melt-electrowriting (MEW) and extrusion-based bioprinting, thereby facilitating three functionalities—the outer layer of MEW-polycaprolactone (PCL) fiber monophasic structure for mechanical integrity, the middle layer of MEW-PCL aligned fibers providing topographical cues for axonal directionality, and the inner bioprinted gelatin methacryloyl layer for encapsulating cells in an ECM-mimicking matrix (~7 kPa stiffness matching nerve tissues). In addition to having tunable mechanical properties (by changing the outer layer design), these biocompatible materials are cost-effective, easily biofabricated, highly tunable for drug-loading, and can support the growth, proliferation, and differentiation of human neural stem cells to peripheral neurons, making the proposed tri-layered NGCs promising candidates for treating long nerve gap injuries.

Expression Patterns of SMAD1–8 in the Peripheral Facial Nerve Following Compressive Nerve Injury or Axotomy

Facial nerve injury can lead to significant functional impairment, emotional impacts, and difficulties in social and economic activities. Although peripheral nerves have the potential for recovery, incomplete regeneration can pose challenges. Suppressor of Mothers Against Decapentaplegic Homolog (SMAD) proteins are crucial in the nerve-regeneration process. The study aimed to investigate the changes in SMAD protein expression involved in peripheral nerve regeneration following facial nerve injury induced by compression or axotomy in a pre-clinical study conducted on Sprague Dawley rats. Facial nerve recovery was assessed at 1, 2, 3, 4, 8, and 12 weeks post-facial nerve compression and axotomy using behavioral tests, including whisker movement and eyelid blink-reflex tests. Additionally, the role of SMAD proteins in the nerve regeneration process was evaluated by analyzing the expression of SMAD1–8 proteins at 2 and 12 weeks post-injury. Behavioral tests revealed significant impairment in facial nerve function in both the Compression and Axotomy groups compared with the Sham group at early time points. Recovery was observed in the Compression group by 2 weeks, whereas the Axotomy group exhibited prolonged impairment through 12 weeks. SMAD protein analyses showed increased expression of SMAD2, SMAD7, and SMAD8 following compression injury, whereas axotomy led to more extensive increases in expression that included SMAD1, SMAD2, SMAD3, SMAD4, SMAD6, SMAD7, and SMAD8. These findings suggest that SMAD proteins play differential roles in nerve regeneration following facial nerve injuries caused by compression versus axotomy. The distinct expression patterns of SMAD proteins highlight their potential as therapeutic targets for enhancing nerve regeneration and functional recovery in peripheral nerve injuries.

CDC42 Regulates the ERK Pathway to Improve Oxygen‒Glucose Deprivation/Reoxygenation-Induced Neural Oxidative Stress and Apoptosis.

CDC42 regulates neural morphology, differentiation, and injury and modifies oxidative stress and neural immune infiltration, but its effect on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neural injury has not been reported. Therefore, this study aimed to investigate the effects of CDC42 overexpression on neural injury and oxidative stress during the OGD/R process. The OGD/R cellular model was established by culturing HT22 cells in glucose-free medium under hypoxic conditions for 2, 4, or 6 h and then transferring them to complete medium and a standard environment for another 24 h. CDC42 and negative control overexpression vectors (oeCDC42 and oeNC) were transfected into HT22 cells; afterwards, PD98059, a specific ERK inhibitor, was added along with or without oeCDC42. CDC42 expression, cell viability, and superoxide dismutase (SOD) activity were reduced, but cell apoptosis and reactive oxygen species (ROS) were elevated after OGD/R induction in a time-dependent manner. oeCDC42 decreased cell apoptosis and ROS and increased SOD activity in OGD/R-induced HT22 cells, but it did not significantly increase cell viability. Moreover, oeCDC42 positively regulated p-ERK and p-c-Fos expression. In addition, PD98059 decreased cell viability and SOD activity but increased cell apoptosis and ROS in OGD/R-induced HT22 cells; moreover, the effects of PD98059 combined with oeCDC42 also showed similar trends compared to oeCDC42 alone regarding the above indexes. CDC42 can ameliorate OGD/R-induced neural oxidative stress and apoptosis by regulating the ERK pathway.

Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia.

Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia.

Selective RNAi silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury

Selective RNAi silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury

Beyond conventional therapies: MSCs in the battle against nerve injury.

Beyond conventional therapies: MSCs in the battle against nerve injury.

The Effect of Acupuncture on the Morphology and Neural Coding Damage of the Central Amygdala in Mice with Chronic Inflammatory Pain and Depression.

Observing the effects and roles of acupuncture on the morphology and neural coding damage of central amygdala (CeA) neurons in chronic inflammatory pain with depression (CIPD) mice and exploring the central nervous mechanism of acupuncture intervention in CIPD. A CIPD model was established by injecting Complete Freund's Adjuvant (CFA) into the left hind foot. Using paw withdrawal latency (PWLs), forced swimming, and open field tests, 40 mice with successfully replicated models were selected and randomly divided into a model group, acupuncture group, and sham acupuncture group, with 12 mice in each group. After treatment, Nissl staining was used to observe the morphology of CeA neurons and the number of Nissl bodies. In vivo multi-channel recordings measured the spontaneous firing frequency, waveform amplitude, inter-spike interval (ISI), and power spectral density (PSD) of CeA neurons. The PWLs in the model and sham acupuncture groups were shortened, the activity time and distance in the central region were reduced, and the forced swimming immobility time increased. The arrangement of CeA neurons is sparse, neurons are damaged, and the number of Nissl bodies is reduced; CeA neurons exhibit abnormal changes in spatiotemporal patterns, with a decrease in spontaneous discharge frequency, discharge amplitude, PSD, and an increase in ISI. The acupuncture group showed prolonged PWLs, increased activity time and distance in the central region, and decreased immobility during forced swimming. The loss of CeA neurons decreased, the cells were arranged neatly, the nucleoli were evident, and the number of Nissl bodies increased. The damage to CeA neural coding was significantly improved, with increased spontaneous discharge frequency, discharge amplitude, PSD, and shortened ISI. Acupuncture may alleviate pain and depressive-like behaviors in CIPD mice and reduce neuronal damage, possibly through mechanisms related to improving the spatiotemporal characteristics of neural coding impairments in the CeA brain region.

Targeting sirtuins in neurological disorders: A comprehensive review.

Targeting sirtuins in neurological disorders: A comprehensive review.

Neuropsychology's Role in Multidisciplinary Follow-Up Care of Neurologically Complex Infants and Toddlers.

Neuropsychology's Role in Multidisciplinary Follow-Up Care of Neurologically Complex Infants and Toddlers.

Trajectories of intrinsic connectivity one year post pediatric mild traumatic brain injury: Neural injury superimposed on neurodevelopment.

Trajectories of intrinsic connectivity one year post pediatric mild traumatic brain injury: Neural injury superimposed on neurodevelopment.