Adult Nerve Research Articles

Unique properties of clinical manifestation and magnetic resonance imaging for differential diagnosis of optic nerve hemangioblastoma.

To investigate the unique properties of clinical manifestation and radiological imaging for differential diagnosis of optic nerve hemangioblastoma (ONH) from adult optic nerve glioma (ONG) prior to surgical resection. ONH and adult ONG patients were recruited from 2012 to 2022. A total of seven ONH patients (8 eyes) and 23 adult ONG patients (24 eyes) were assessed. The median onset age of ONH patients was older than that of adult ONG patients (p = 0.007). There were 42.9% (3/7) of ONH patients closely associated with the diagnosis of Von Hippel-Lindau (VHL) syndrome. Notably in Magnetic Resonance Imaging (MRI), the retrobulbar hemangioblastomas in all ONH patients were primarily intraorbital (100%, 8/8), canalicular (87.5%, 7/8), and anterior intracranial (12.5%, 1/8), especially concentrated in the orbital apex, with little posterior optic pathway involvement. Nearly all affected parts of optic nerve in the ONH group (75.0%, 6/8) presented with circumscribed cystic-solid components, characterized by cystic lesions (peritumoral oedema) anteriorly and solid tumours posteriorly, with significant heterogeneous enhancement. Adult ONG lesions prior to extend from the anterior portion to the whole length of the optic nerve, with relatively innocent enlargement in the postcontrast study. Optic nerve tumours in those with older ages at diagnosis (>30 years) or those diagnosed with VHL syndrome are more likely to be indicative of ONH. In the absence of associated VHL syndrome, a distinguishing MRI feature is the concentration of tumours in the orbital apex, characterized by circumscribed cystic-solid components and heterogeneous enhancement of the solid portion.

Quantitation of the physicochemical properties of myelin using Nile Red fluorescence spectroscopy.

Myelin is a vital structure that is key to rapid saltatory conduction in the central and peripheral nervous systems. Much work has been done over the decades examining the biochemical composition and morphology of myelin at the light and electron microscopic levels. Here we report a method to study myelin based on the fluorescent probe Nile Red. This lipophilic dye readily partitions into live and chemicallyfixed myelin producing bright, well-resolved images of the sheath. Using spectral confocal microscopy, a complete emission spectrum of Nile Red fluorescence can be acquired for each pixel in an image. The solvatochromic properties of Nile Red cause its emission spectrum to change depending on the polarity of its local environment. Therefore, measuring spectral shifts can report subtle changes in the physicochemical properties of myelin. We show differences in myelin polarity in central versus peripheral nervous system and in different regions of central nervous system white matter of the mouse brain, together with developmental and sex variations. This technique is also well suited for measuring subtle changes in myelin properties in live exvivo white matter specimens. We also demonstrate how light deprivation induces a myelin polarity change in adult mouse optic nerve underscoring a continuing myelin plasticity in response to axonal activity well into adulthood. The Nile Red spectroscopic method allows measurement of subtle physicochemical changes in myelin that can importantly influence its electrical properties and by extension, conduction velocities in axons.

Multi-Channel Microscale Nerve Cuffs for Spatially Selective Neuromodulation.

Peripheral nerve modulation via electrical stimulation shows promise for treating several diseases, but current approaches lack selectivity, leading to side effects. Exploring selective neuromodulation with commercially available nerve cuffs is impractical due to their high cost and limited spatial resolution. While custom cuffs reported in the literature achieve high spatial resolutions, they require specialized microfabrication equipment and significant effort to produce even a single design. This inability to rapidly and cost-effectively prototype novel cuff designs impedes research into selective neuromodulation therapies in acute studies. To address this, we developed a reproducible method to easily create multi-channel epineural nerve cuffs for selective fascicular neuromodulation. Leveraging commercial flexible printed circuit (FPC) technology, we created cuffs with high spatial resolution (50 μm) and customizable parameters like electrode size, channel count, and cuff diameter. We designed cuffs to accommodate adult mouse or rat sciatic nerves (300-1500 μm diameter). We coated the electrodes with PEDOT:PSS to improve the charge injection capacity. We demonstrated selective neuromodulation in both rats and mice, achieving preferential activation of the tibialis anterior (TA) and lateral gastrocnemius (LG) muscles. Selectivity was confirmed through micro-computed tomography (μCT) and quantified through a selectivity index. These results demonstrate the potential of this fabrication method for enabling selective neuromodulation studies while significantly reducing production time and costs compared to traditional approaches.

Challenges in advancing Schwann cell transplantation for spinal cord injury repair

Background AimsIn this article we aimed to provide an expert synthesis of the current status of Schwann cell (SC)therapeutics and potential steps to increase their clinical utility. MethodsWe provide an expert synthesis based on preclinical, clinical and manufacturing experience. ResultsSchwann cells (SCs) are essential for peripheral nerve regeneration and are of interest in supporting axonal repair after spinal cord injury (SCI). SCs can be isolated and cultivated in tissue culture from adult nerve biopsies or generated from precursors and neural progenitors using specific differentiation protocols leading to expanded quantities. In culture, they undergo dedifferentiation to a state similar to “repair” SCs. The known repertoire of SC functions is increasing beyond axon maintenance, myelination, and axonal regeneration to include immunologic regulation and the release of potentially therapeutic extracellular vesicles. Recently, autologous human SC cultures purified under cGMP conditions have been tested in both nerve repair and subacute and chronic SCI clinical trials. Although the effects of SCs to support nerve regeneration are indisputable, their efficacy for clinical SCI has been limited according to the outcomes examined. ConclusionsThis review discusses the current limitations of transplanted SCs within the damaged spinal cord environment. Limitations include limited post-transplant cell survival, the inability of SCs to migrate within astrocytic parenchyma, and restricted axonal regeneration out of SC-rich graft regions. We describe steps to amplify the survival and integration of transplanted SCs and to expand the repertoire of uses of SCs, including SC-derived extracellular vesicles. The relative merits of transplanting autologous versus allogeneic SCs and the role that endogenous SCs play in spinal cord repair are described. Finally, we briefly describe the issues requiring solutions to scale up SC manufacturing for commercial use.

Connectomic reconstruction of a female Drosophila ventral nerve cord.

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophilamelanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographicnanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.

Collaborative Roles for RAC1, ERM Proteins and PTEN During Adult Sensory Axon Regeneration.

The role of local of growth cone (GC) manipulation in adult regenerative systems is largely unexplored despite substantial translational importance. Here we investigated collaboration among Rac1 GTPase, its partnering ERM proteins and PTEN in adult sensory neurons and adult nerve regeneration. We confirmed expression of both Rac1 and ERM in adults and noted substantial impacts on neurite outgrowth in naïve and pre-injured adult sensory neurons. PTEN inhibition added to this outgrowth. Rac1 activation acted directly on adult GCs facilitating both attractive turning and advancement. In vivo regeneration indices including electrophysiological recovery, return of sensation, walking, repopulation of myelinated axons and reinnervation of the target epidermis indicated benefits of local Rac1 activation. These indices suggested maximal GC activation whereas local PTEN inhibition offered only limited added improvement. Our findings provide support for the concept of manipulating adult GCs, by emphasizing local Rac1 activation in directing therapy for nerve repair.

Neuronal segmentation in cephalopod arms.

The prehensile arms of the cephalopod are among these animals most remarkable features, but the neural circuitry governing arm and sucker movements remains largely unknown. We studied the neuronal organization of the adult axial nerve cord (ANC) of Octopus bimaculoides with molecular and cellular methods. The ANCs, which lie in the center of every arm, are the largest neuronal structures in the octopus, containing four times as many neurons as found in the central brain. In transverse cross section, the cell body layer (CBL) of the ANC wraps around its neuropil (NP) with little apparent segregation of sensory and motor neurons or nerve exits. Strikingly, when studied in longitudinal sections, the ANC is segmented. ANC neuronal cell bodies form columns separated by septa, with 15 segments overlying each pair of suckers. The segments underlie a modular organization to the ANC neuropil: neuronal cell bodies within each segment send the bulk of their processes directly into the adjoining neuropil, with some reaching the contralateral side. In addition, some nerve processes branch upon entering the NP, forming short-range projections to neighboring segments and mid-range projections to the ANC segments of adjoining suckers. The septa between the segments are employed as ANC nerve exits and as channels for ANC vasculature. Cellular analysis establishes that adjoining septa issue nerves with distinct fiber trajectories, which across two segments (or three septa) fully innervate the arm musculature. Sucker nerves also use the septa, setting up a nerve fiber "suckerotopy" in the sucker-side of the ANC. Comparative anatomy suggests a strong link between segmentation and flexible sucker-laden arms. In the squid Doryteuthis pealeii, the arms and the sucker-rich club of the tentacles have segments, but the sucker-poor stalk of the tentacles does not. The neural modules described here provide a new template for understanding the motor control of octopus soft tissues. In addition, this finding represents the first demonstration of nervous system segmentation in a mollusc.

Cultivation of Schwann cells from fresh and non-fresh adult equine peripheral nerves

BackgroundOver the past 25 years, acquired equine polyneuropathy (AEP) has emerged as a neurological disease in Scandinavian horses. This condition is characterized by histopathological features including the presence of Schwann cell (SC) inclusions. Cultivated equine SCs would serve as a valuable resource for investigations of factors triggering this Schwannopathy. Ideally, cells should be sampled for cultivation from fresh nerves immediately after death of the animal, however the availability of fresh material is limited, due to the inconsistent case load and the inherent technical and practical challenges to collection of samples in the field. This study aimed to cultivate SCs from adult equine peripheral nerves and assess their ability to survive in sampled nerve material over time to simulate harvesting of SCs in field situations. New methodsPeripheral nerves from five non-neurological horses were used. After euthanasia, both fresh and non-fresh nerve samples were harvested from each horse. Flow cytometry was employed to confirm the cellular identity and to determine the SC purity. ResultsThe results revealed successful establishment of SC cultures from adult equine peripheral nerves, with the potential to achieve high SC purity from both fresh and non-fresh nerve samples. Comparison with existing methodWhile most SC isolation methods focus on harvest of cells from fresh nerve materials from laboratory animals, our approach highlights the possibility of utilizing SC cultures from field-harvested and transported nerve samples from horses. ConclusionsWe describe a method for isolating SCs with high purity from both fresh and non-fresh peripheral nerves of adult horses.

Immunohistochemical phenotype of sensory neurons associated with sympathetic plexuses in the trigeminal ganglia of adult nerve growth factor transgenic mice.

Following peripheral nerve injury, postganglionic sympathetic axons sprout into the affected sensory ganglia and form perineuronal sympathetic plexuses with somata of sensory neurons. This sympathosensory coupling contributes to the onset and persistence of injury-induced chronic pain. We have documented the presence of similar sympathetic plexuses in the trigeminal ganglia of adult mice that ectopically overexpress nerve growth factor (NGF), in the absence of nerve injury. In this study, we sought to further define the phenotype(s) of these trigeminal sensory neurons having sympathetic plexuses in our transgenic mice. Using quantitative immunofluorescence staining analyses, we show that the invading sympathetic axons specifically target sensory somata immunopositive for several biomarkers: NGF high-affinity receptor tyrosine kinase A (trkA), calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NFH), and P2X purinoceptor 3 (P2X3). Based on these phenotypic characteristics, the majority of the sensory somata surrounded by sympathetic plexuses are likely to be NGF-responsive nociceptors (i.e., trkA expressing) that are peptidergic (i.e., CGRP expressing), myelinated (i.e., NFH expressing), and ATP sensitive (i.e., P2X3 expressing). Our data also show that very few sympathetic plexuses surround sensory somata expressing other nociceptive (pain) biomarkers, including substance P and acid-sensing ion channel 3. No sympathetic plexuses are associated with sensory somata that display isolectin B4 binding. Though the cellular mechanisms that trigger the formation of sympathetic plexus (with and without nerve injury) remain unknown, our new observations yield an unexpected specificity with which invading sympathetic axons appear to target a precise subtype of nociceptors. This selectivity likely contributes to pain development and maintenance associated with sympathosensory coupling.

Nerve Regeneration with a Scaffold Incorporating an Absorbable Zinc-2% Iron Alloy Filament to Improve Axonal Guidance.

Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair.

Application and underlying mechanism of acupuncture for the nerve repair after peripheral nerve injury: remodeling of nerve system.

Peripheral nerve injury (PNI) is a structural event with harmful consequences worldwide. Due to the limited intrinsic regenerative capacity of the peripheral nerve in adults, neural restoration after PNI is difficult. Neurological remodeling has a crucial effect on the repair of the form and function during the regeneration of the peripheral nerve after the peripheral nerve is injured. Several studies have demonstrated that acupuncture is effective for PNI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve the nervous system remodeling in the process of nerve repair. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating related neurotrophins retrograde transport, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), N-cadherin, and MicroRNAs. Peripheral nerve injury enhances the perceptual response of the central nervous system to pain, causing central sensitization and accelerating neuronal cell apoptosis. Together with this, the remodeling of synaptic transmission function would worsen pain discomfort. Neuroimaging studies have shown remodeling changes in both gray and white matter after peripheral nerve injury. Acupuncture not only reverses the poor remodeling of the nervous system but also stimulates the release of neurotrophic substances such as nerve growth factors in the nervous system to ameliorate pain and promote the regeneration and repair of nerve fibers. In conclusion, the neurological remodeling at the peripheral and central levels in the process of acupuncture treatment accelerates nerve regeneration and repair. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of PNI.

Long latency reflexes of the median nerves in healthy adults.

Long latency reflexes (LLRs) are late responses in nerve conduction studies seen after peripheral nerve stimulation during submaximal muscle contraction. They follow a short latency reflex, also known as the H reflex, and are thought to involve transcortical pathways, providing a measure of proximal nerve and central conduction. For this reason, they have been evaluated in several central nervous system diseases, but reference values are not widely published and are mostly based on old studies with very small numbers of participants. Therefore, in this work we aim to provide comprehensive reference values for LLR testing. LLRs were tested in a cohort of 100 healthy participants, testing the median nerve bilaterally. Mean latencies for short latency reflex (SLR), LLR1, LLR2, and LLR3 were 27.00, 38.50, 47.60, and 67.34 milliseconds, respectively. The allowable side-to-side difference was approximately 3 to 4 milliseconds. No significant sex-related differences were seen. Height correlated moderately with the SLR latency, but only weakly with LLR1, LLR2, and LLR3. This work provides normal LLR values for comparison with future studies in disease. The technique used may allow for improved evaluation of central nervous system or proximal peripheral nerve disorders.

Analysis of the improvement in monocular amblyopia visual acuity caused by the changes in non-amblyopia visual acuity in 74 adults.

To observe the clinical phenomenon of amblyopia vision improvement in patients with monocular amblyopia over 18 years old after non-amblyopia diseases, analyze the conditions and causes of vision improvement, explore the plasticity of the adult optic nerve, and provide a clinical basis for the treatment of adult amblyopia. A total of 74 patients with monocular amblyopia combined with non-amblyopia visual acuity decline from 2018 to 2021 were collected. The patient's age, initial best-corrected visual acuity (BCVA), pattern visual evoked potential examination results, and visual acuity regression were recorded. The BCVA of amblyopia was recorded every 3 months using an early treatment of diabetic retinopathy study visual acuity chart. In the 3rd month, BCVA increased by 16.2%, reaching 98% in the 9th month and 100% in the 12th months. According to the age of patients, the group aged 18 to 35 years was better than the group aged 35 to 60 years, whereas the group aged 35 to 60 years was better than the group aged over 60 years (P < .05). According to the comparison of initial visual acuity, the BCVA of the < 5 letter group was lower than that of the other 2 groups (P < .05). According to the pattern visual evoked potential results, the peak time of the < 10 ms group was better than that of the 10 to 20 ms group; the 10 to 20 ms group was better than that of the > 20 ms group; the peak decrease of the < 30% group was better than that of the 30% to 50% group; and the 30% to 50% group was better than that of the > 50% group (P < .05). The visual acuity regression of amblyopia in the 0.5 to 1-year group was higher than that in the other 2 groups (P < .05). This study confirms that adult amblyopia can still be cured under certain conditions. This visual plasticity is related to age, initial visual acuity, and excitability of the visual center. This study provides new clinical evidence and diagnostic ideas for the study of the pathogenesis of adult amblyopia.

Visual rehabilitation indicating neuroplasticity in an esotropic adult patient with diplopia after sudden visual acuity loss in the non-amblyopic eye: A case report.

The aim of this case report is to present the successful management of both diplopia and amblyopia in a specific clinical situation, demonstrating neuroplasticity of the visual system in an adult patient. Causes of diplopia include eye pathologies in monocular diplopia and ischemic ocular motor nerve palsies, sudden life-threatening and chronic conditions in central nervous system in binocular diplopia. Strabismic amblyopia and nonarteritic anterior ischemic optic neuropathy are quite often ophthalmic conditions, first one is caused by suppression during developmental period and the latter one by ischemia of the optic nerve in adults. Coexistence of aforementioned conditions may cause unusual clinical situation in which ability of nervous system to functional reorganization could be demonstrated. In our adult patient, diplopia was incited by the loss of suppression of the strabismic amblyopic eye, which was the consequence of a sudden decrease of the visual acuity in the previously better eye in the course of nonarteritic anterior ischemic optic neuropathy. This led to impairment in daily activities. Visual training rehabilitation improved distance and near visual acuity in the amblyopic eye over three months, and prescribing two pairs of glasses with prisms enabled the patient to return to daily activities. The discussed patient lost the suppression of the strabismic amblyopic eye. Management of amblyopia is usually undertaken in children, however considering neuroplasticity we successfully attempted to improve visual functioning of our patient, despite lower intensity of neuroplasticity functions in an adult brain.

Photons Induce Vesicular Exocytotic Release of Glutamate in a Power-Dependent Way

Increasing evidence indicates that photobiomodulation, based on tissue irradiation with photons in the red to near-infrared spectrum, may be an effective therapeutic approach to central nervous system disorders. Although nervous system functionality has been shown to be affected by photons in animal models, as well as in preliminary evidence in healthy subjects or in patients with neuropsychiatric disorders, the mechanisms involved in the photobiomodulation effects have not yet been clarified. We previously observed that photobiomodulation could stimulate glutamate release. Here, we investigate mechanisms potentially involved in the glutamate-releasing effect of photons from adult mouse cerebrocortical nerve terminals. We report evidence of photon ability to induce an exocytotic vesicular release of glutamate from the terminals of glutamatergic neurons in a power-dependent way. It can be hypothesized that photobiomodulation, depending on the potency, can release glutamate in a potentially neurotoxic or physiological range.

Schwann cells and myelin in human peripheral nerve: Major protein components vary with age, axon size and pathology.

We examined major protein components of Schwann cells (SCs) and myelin in normal and diseased human peripheral nerves. We evaluated distributions of neural cell adhesion molecule (NCAM), P0 protein (P0) and myelin basic protein (MBP) in frozen sections of 98 sural nerves. Non-myelinating SC in normal adults contained NCAM, but not P0 or MBP. With chronic axon loss, SC without associated axons (Büngner band cells) often co-stained for both NCAM and P0. Onion bulb cells also co-stained for both P0 and NCAM. Infants had many SC with MBP but no P0. All myelin sheaths contained P0. Myelin around large, and some intermediate-sized, axons co-stained for both MBP and P0. Myelin on other intermediate-sized axons had P0, but no MBP. Regenerated axons often had sheaths with MBP, P0 and some NCAM. During active axon degeneration, myelin ovoids often co-stained for MBP, P0 and NCAM. Demyelinating neuropathy patterns included SC (NCAM) loss, and myelin with abnormally distributed, or reduced, P0. Peripheral nerve SC and myelin have varied molecular phenotypes, related to age, axon size and nerve pathology. In normal adult peripheral nerve, myelin has two different patterns of molecular composition. MBP is mostly absent from myelin around a population of intermediate-sized axons, whereas P0 is present in myelin around all axons. Denervated SCs have a molecular signature that differs from normal SC types. With acute denervation, SCs may stain for both NCAM and MBP. Chronically denervated SCs often stain for both NCAM and P0.

Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits.

Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function.SIGNIFICANCE STATEMENT Oligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional significance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manipulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent manner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration, along with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin generation in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promoting OL generation might be a promising strategy to preserve visual function from age-related decline.

Effects of Altering Magnesium Metal Surfaces on Degradation In Vitro and In Vivo during Peripheral Nerve Regeneration.

In vivo use of biodegradable magnesium (Mg) metal can be plagued by too rapid a degradation rate that removes metal support before physiological function is repaired. To advance the use of Mg biomedical implants, the degradation rate may need to be adjusted. We previously demonstrated that pure Mg filaments used in a nerve repair scaffold were compatible with regenerating peripheral nerve tissues, reduced inflammation, and improved axonal numbers across a short-but not long-gap in sciatic nerves in rats. To determine if the repair of longer gaps would be improved by a slower Mg degradation rate, we tested, in vitro and in vivo, the effects of Mg filament polishing followed by anodization using plasma electrolytic oxidation (PEO) with non-toxic electrolytes. Polishing removed oxidation products from the surface of as-received (unpolished) filaments, exposed more Mg on the surface, produced a smoother surface, slowed in vitro Mg degradation over four weeks after immersion in a physiological solution, and improved attachment of cultured epithelial cells. In vivo, treated Mg filaments were used to repair longer (15 mm) injury gaps in adult rat sciatic nerves after placement inside hollow poly (caprolactone) nerve conduits. The addition of single Mg or control titanium filaments was compared to empty conduits (negative control) and isografts (nerves from donor rats, positive control). After six weeks in vivo, live animal imaging with micro computed tomography (micro-CT) showed that Mg metal degradation rates were slowed by polishing vs. as-received Mg, but not by anodization, which introduced greater variability. After 14 weeks in vivo, functional return was seen only with isograft controls. However, within Mg filament groups, the amount of axonal growth across the injury site was improved with slower Mg degradation rates. Thus, anodization slowed degradation in vitro but not in vivo, and degradation rates do affect nerve regeneration.

Deficient deposition of new myelin impairs adult optic nerve function in a murine model of diabetes.

Visual impairment in diabetes is a growing public health concern. Apart from the well-defined diabetic retinopathy, disturbed optic nerve function, which is dependent on the myelin sheath, has recently been recognized as an early feature of visual impairment in diabetes. However, the underlying cellular mechanisms remain unclear. Using a streptozotocin-induced diabetic mouse model, we observed a myelin deficiency along with a disturbed composition of oligodendroglial lineage cells in diabetic optic nerve. We found that new myelin deposition, a continuous process that lasts throughout adulthood, was diminished during pathogenesis. Genetically dampening newly generated myelin by conditionally deleting olig2 in oligodendrocyte precursor cells within this short time window extensively delayed the signal transmission of the adult optic nerve. In addition, clemastine, an antimuscarinic compound that enhances myelination, significantly restored oligodendroglia, and promoted the functional recovery of the optic nerve in diabetic mice. Together, our results point to the role of new myelin deposition in optic neuropathy under diabetic insult and provide a promising therapeutic target for restoring visual function.

Sonographic peripheral nerve cross-sectional area in adults, excluding median and ulnar nerves: A systematic review and meta-analysis.

Although electromyography remains the "gold standard" for assessing and diagnosing peripheral nerve disorders, ultrasound has emerged as a useful adjunct, providing valuable anatomic information. The objective of this study was to conduct a systematic review and meta-analysis evaluating the normative sonographic values for adult peripheral nerve cross-sectional area (CSA). Medline and Cochrane Library databases were systematically searched for healthy adult peripheral nerve CSA, excluding the median and ulnar nerves. Data were meta-analyzed, using a random-effects model, to calculate the mean nerve CSA and its 95% confidence interval (CI) for each nerve at a specific anatomical location (= group). Thirty groups were identified and meta-analyzed, which comprised 16 from the upper extremity and 15 from the lower extremity. The tibial nerve (n=2916 nerves) was reported most commonly, followed by the common fibular nerve (n=2580 nerves) and the radial nerve (n=2326 nerves). Means and 95% confidence interval (CIs) of nerve CSA for the largest number of combined nerves were: radial nerve assessed at the spiral groove (n=1810; mean,5.14 mm2 ; 95% CI,4.33 to 5.96); common fibular nerve assessed at the fibular head (n=1460; mean,10.18 mm2 ; 95% CI,8.91 to 11.45); and common fibular nerve assessed at the popliteal fossa (n=1120; mean,12.90 mm2 ; 95% CI,9.12 to 16.68). Publication bias was suspected, but its influence on the results was minimal. Two hundred thirty mean CSAs from 15 857 adult nerves are included in the meta-analysis. These are further categorized into 30 groups, based on anatomical location, providing a comprehensive reference for the clinician and researcher investigating adult peripheral nerve anatomy.