Structure of the oral tentacles of early ontogeny stage in brachiopod Hemithiris psittacea (Rhynchonelliformea, Rhynchonellida).

Brachiopods have the most complex lophophore in comparison with other lophophorates, i.e., phoronids and bryozoans. However, at early ontogenetic stages, brachiopods have a lophophore of simple morphology, which consists of the oral tentacles. Data on the ultrastructure of the oral tentacles is mostly missing. Nonetheless, it has recently been suggested that the structure of oral tentacles is ancestral for all lophophorates in general, and for brachiopods in particular. The fine structure of the oral tentacles in the brachiopod Hemithiris psittacea is studied using light microscopy, transmission and scanning electron microscopy, cytochemistry and confocal laser scanning microscopy. The oral tentacles have a round shape in transverse section, and four ciliary zones, i.e., one frontal, two lateral, and one abfrontal. Latero-frontal sensory cells occur among the frontal epithelium. Four basiepithelial nerves in the ciliary epithelium are colocalized with ciliary zones. Lophophores of simple morphology in phoronids and brachiopods are characterized by non-specified round forms of tentacles. In phoronids and bryozoans, tentacles have additional latero-frontal ciliary zones that function as a sieve during filtration. In most brachiopods, lateral cilia are involved in the capture of food particles, whereas latero-frontal cells are retained in the frontal zone as sensory elements. The oral tentacles of H. psittacea contain a coelomic canal and have distinct frontal and abfrontal longitudinal muscles, which are separated from each other by peritoneal cells. A similar structure of tentacle muscles occurs in all bryozoans, whereas in phoronids, the frontal and abfrontal tentacle muscles are not separated by peritoneal cells. We suggest that the lophophorates' ancestor had tentacles, which were similar to the tentacles of some phoronids with lophophore of simple morphology. We also assume that the structure of the oral tentacles is ancestral for all brachiopods and the specialization of brachiopod tentacles correlates with the appearance of the double row of tentacles.

Galvanic vs. pulsatile effects on decision-making networks: reshaping the neural activation landscape.

Objective. Primarily due to safety concerns, biphasic pulsatile stimulation (PS) is the present standard for electrical excitation of neural tissue with a diverse set of applications. While pulses have been shown to be effective to achieve functional outcomes, they have well-known deficits. Due to recent technical advances, galvanic stimulation (GS), delivery of current for extended periods of time (>1 s), has re-emerged as an alternative to PS.Approach. In this paper, we use a winner-take-all decision-making cortical network model to investigate differences between pulsatile and GS in the context of a perceptual decision-making task.Main results. Based on previous work, we hypothesized that GS would produce more spatiotemporally distributed, network-sensitive neural responses, while PS would produce highly synchronized activation of a limited group of neurons. Our results in-silico support these hypotheses for low-amplitude GS but deviate when galvanic amplitudes are large enough to directly activate or block nearby neurons.Significance. We conclude that with careful parametrization, GS could overcome some limitations of PS to deliver more naturalistic firing patterns in the group of targeted neurons.

Enhancing neuroinduction activity of PLCL-based nerve conduits through native epineurium integration.

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation.

Advancing spinal cord injury care through non-invasive autonomic dysreflexia detection with AI.

This paper presents an AI-powered solution for detecting and monitoring Autonomic Dysreflexia (AD) in individuals with spinal cord injuries. Current AD detection methods are limited, lacking non-invasive monitoring systems. We propose a model that combines skin nerve activity (SKNA) signals with a deep neural network (DNN) architecture to overcome this limitation. The DNN is trained on a meticulously curated dataset obtained through controlled colorectal distension, inducing AD events in rats with spinal cord surgery above the T6 level. The proposed system achieves an impressive average classification accuracy of 93.9% ± 2.5%, ensuring accurate AD identification with high precision (95.2% ± 2.1%). It demonstrates a balanced performance with an average F1 score of 94.4% ± 1.8%, indicating a harmonious balance between precision and recall. Additionally, the system exhibits a low average false-negative rate of 4.8% ± 1.6%, minimizing the misclassification of non-AD cases. The robustness and generalizability of the system are validated on unseen data, maintaining high accuracy, F1 score, and a low false-negative rate. This AI-powered solution represents a significant advancement in non-invasive, real-time AD monitoring, with the potential to improve patient outcomes and enhance AD management in individuals with spinal cord injuries. This research contributes a promising solution to the critical healthcare challenge of AD detection and monitoring.

Bioprinting functional neural networks.

3D printing human tissue models derived from stem cells provides an increasingly popular tissue engineering strategy for probing biological questions. Here Yan et al.1 demonstrate how this technology can be used to model mature human neural tissues with functional neural networks in healthy and disease states.

3D bioprinting of human neural tissues with functional connectivity.

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate into neurons and form functional neural circuits within and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents, and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.

Tumor Neurobiology in the Pathogenesis and Therapy of Head and Neck Cancer.

The neurobiology of tumors has attracted considerable interest from clinicians and scientists and has become a multidisciplinary area of research. Neural components not only interact with tumor cells but also influence other elements within the TME, such as immune cells and vascular components, forming a polygonal relationship to synergistically facilitate tumor growth and progression. This review comprehensively summarizes the current state of the knowledge on nerve-tumor crosstalk in head and neck cancer and discusses the potential underlying mechanisms. Several mechanisms facilitating nerve-tumor crosstalk are covered, such as perineural invasion, axonogenesis, neurogenesis, neural reprogramming, and transdifferentiation, and the reciprocal interactions between the nervous and immune systems in the TME are also discussed in this review. Further understanding of the nerve-tumor crosstalk in the TME of head and neck cancer may provide new nerve-targeted treatment options and help improve clinical outcomes for patients.

Comparative analysis of supercritical fluid-based and chemical-based decellularization techniques for nerve tissue regeneration.

Axon regeneration and Schwann cell proliferation are critical processes in the repair and functional recovery of damaged neural tissues. Biomaterials can play a crucial role in facilitating cell proliferative processes that can significantly impact the target tissue repair. Chemical decellularization and supercritical fluid-based decellularization methods are similar approaches that eliminate DNA from native tissues for tissue-mimetic biomaterial production by using different solvents and procedures to achieve the final products. In this study, we conducted a comparative analysis of these two methods in the context of nerve regeneration and neuron cell differentiation efficiency. We evaluated the efficacy of each method in terms of biomaterial quality, preservation of extracellular matrix components, promotion of neuronal cell differentiation and nerve tissue repair ability in vivo. Our results indicate that while both methods produce high-quality biomaterials, supercritical fluid-based methods have several advantages over conventional chemical decellularization, including better preservation of extracellular matrix components and mechanical properties and superior promotion of cellular responses. We conclude that supercritical fluid-based methods show great promise for biomaterial production for nerve regeneration and neuron cell differentiation applications.

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation.

OBJECTIVE: Photobiomodulation at higher irradiances has great potential as a pain-alleviating method that selectively inhibits small diameter nerve fibers and corresponding sensory experiences, such as nociception and heat sensation. The longevity and magnitude of these effects as a function of laser irradiation parameters at the nerve was explored. METHODS: In a rodent chronic pain model (spared nerve injury-SNI), light was applied directly at the sural nerve with four delivery schemes: two irradiance levels (7.64 and 2.55 W/cm2 ) for two durations each, corresponding to either 4.8 or 14.4 J total energy, and the effect on sensory hypersensitivities was evaluated. RESULTS: At emitter irradiances of 7.64 W/cm2 (for 240 s), 2.55 W/cm2 (for 720 s), and 7.64 W/cm2 (for 80 s) the heat hypersensitivity was relieved the day following photobiomodulation (PBM) treatment by 37 ± 8.1% (statistically significant, p < 0.001), 26% ± 6% (p = 0.072), and 28 ± 6.1% (statistically significant, p = 0.032), respectively, and all three treatments reduced the hypersensitivity over the course of the experiment (13 days) at a statistically significant level (mixed-design analysis of variance, p < 0.05). The increases in tissue temperature (5.3 ± 1.0 and 1.3 ± 0.4°C from 33.3°C for the higher and lower power densities, respectively) at the neural target were well below those typically associated with permanent action potential disruption. CONCLUSIONS: The data from this study support the use of direct PBM on nerves of interest to reduce sensitivities associated with small-diameter fiber activity.

Calcitonin gene-related peptide regulates periodontal tissue regeneration.

Calcitonin gene-related peptide (CGRP), a neuropeptide composed of 37 amino acids secreted from the sensory nerve endings, reportedly possesses various physiological effects, such as vasodilation and neurotransmission. Recently, there have been increasing reports of the involvement of CGRP in bone metabolism; however, its specific role in the pathogenesis of periodontitis, particularly in the repair and healing processes, remains to be elucidated. Therefore, this study aimed to investigate dynamic expression patterns of CGRP during the destruction and regeneration processes of periodontal tissues in a mouse model of experimental periodontitis. We also explored the effects of CGRP on periodontal ligament cells, which can differentiate to hard tissue-forming cells (cementoblasts or osteoblasts). Our findings demonstrated that CGRP stimulation promotes the differentiation of periodontal ligament cells into hard tissue-forming cells. Experimental results using a ligature-induced periodontitis mouse model also suggested fluctuations in CGRP expression during periodontal tissue healing, underscoring the vital role of CGRP signaling in alveolar bone recovery. The study results highlight the important role of nerves in the periodontal ligament not only in sensory reception in the periphery, as previously known, but also in periodontal tissue homeostasis and tissue repair processes.

Reactive Gliosis in Neonatal Disorders: Friend or Foe for Neuroregeneration?

A developing nervous system is particularly vulnerable to the influence of pathophysiological clues and injuries in the perinatal period. Astrocytes are among the first cells that react to insults against the nervous tissue, the presence of pathogens, misbalance of local tissue homeostasis, and a lack of oxygen and trophic support. Under this background, it remains uncertain if induced astrocyte activation, recognized as astrogliosis, is a friend or foe for progressing neonatal neurodevelopment. Likewise, the state of astrocyte reactivity is considered one of the key factors discriminating between either the initiation of endogenous reparative mechanisms compensating for aberrations in the structures and functions of nervous tissue or the triggering of neurodegeneration. The responses of activated cells are modulated by neighboring neural cells, which exhibit broad immunomodulatory and pro-regenerative properties by secreting a plethora of active compounds (including interleukins and chemokines, neurotrophins, reactive oxygen species, nitric oxide synthase and complement components), which are engaged in cell crosstalk in a paracrine manner. As the developing nervous system is extremely sensitive to the influence of signaling molecules, even subtle changes in the composition or concentration of the cellular secretome can have significant effects on the developing neonatal brain. Thus, modulating the activity of other types of cells and their interactions with overreactive astrocytes might be a promising strategy for controlling neonatal astrogliosis.

Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration.

Aging is a complex multifactorial process that results in tissue function impairment across the whole organism. One of the common consequences of this process is the loss of muscle mass and the associated decline in muscle function, known as sarcopenia. Aging also presents with an increased risk of developing other pathological conditions such as neurodegeneration. Muscular and neuronal degeneration cause mobility issues and cognitive impairment, hence having a major impact on the quality of life of the older population. The development of novel therapies that can ameliorate the effects of aging is currently hindered by our limited knowledge of the underlying mechanisms and the use of models that fail to recapitulate the structure and composition of the cell microenvironment. The emergence of bioengineering techniques based on the use of biomimetic materials and biofabrication methods has opened the possibility of generating 3D models of muscular and nervous tissues that better mimic the native extracellular matrix. These platforms are particularly advantageous for drug testing and mechanistic studies. In this review, we discuss the developments made in the creation of 3D models of aging-related neuronal and muscular degeneration and we provide a perspective on the future directions for the field.

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

BACKGROUND: Over 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 METHODS: Peripheral 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. RESULTS: The 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 METHOD: While 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. CONCLUSIONS: We describe a method for isolating SCs with high purity from both fresh and non-fresh peripheral nerves of adult horses.

Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

State of the Art and Current Challenges on Electroactive Biomaterials and Strategies for Neural Tissue Regeneration.

The loss or failure of an organ/tissue stands as one of the healthcare system's most prevalent, devastating, and costly challenges. Strategies for neural tissue repair and regeneration have received significant attention due to their particularly strong impact on patients' well-being. Many research efforts are dedicated not only to control the disease symptoms but also to find solutions to repair the damaged tissues. Neural tissue engineering (TE) plays a key role in addressing this problem and significant efforts are being carried out to develop strategies for neural repair treatment. In the last years, active materials allowing to tune cell-materials interaction are being increasingly used, representing a recent paradigm in TE applications. Among the most important stimuli influencing cell behavior are the electrical and mechanical ones. In this way, materials with the ability to provide this kind of stimuli to the neural cells seem to be appropriate to support neural TE. In this scope, this review summarizes the different biomaterials types used for neural TE, highlighting the relevance of using active biomaterials and electrical stimulation. Furthermore, this review provides not only a compilation of the most relevant studies and results but also strategies for novel and more biomimetic approaches for neural TE.

Myostatin and CXCL11 promote nervous tissue macrophages to maintain osteoarthritis pain.

Pain is the most debilitating symptom of knee osteoarthritis (OA) that can even persist after total knee replacement. The severity and duration of pain do not correlate well with joint tissue alterations, suggesting other mechanisms may drive pain persistence in OA. Previous work identified that macrophages accumulate in the dorsal root ganglia (DRG) containing the somas of sensory neurons innervating the injured knee joint in a mouse OA model and acquire a M1-like phenotype to maintain pain. Here we aimed to unravel the mechanisms that govern DRG macrophage accumulation and programming. The accumulation of F4/80+iNOS+ (M1-like) DRG macrophages was detectable at day 3 after mono-iodoacetate (MIA)-induced OA in the mouse. Depletion of macrophages prior to induction of OA resolved pain-like behaviors by day 7 without affecting the initial development of pain-like behaviors. Analysis of DRG transcript identified CXCL11 and myostatin. CXCL11 and myostatin were increased at 3 weeks post OA induction, with CXCL11 expression partially localized in satellite glial cells and myostatin in sensory neurons. Blocking CXCL11 or myostatin prevented the persistence of OA pain, without affecting the initiation of pain. CXCL11 neutralization reduced the number of total and F4/80+iNOS+ DRG macrophages, whilst myostatin inhibition diminished the programming of F4/80+iNOS+ DRG macrophages. Intrathecal injection of recombinant CXCL11 did not induce pain-associated behaviors. In contrast, intrathecal myostatin increased the number of F4/80+iNOS+ DRG macrophages concurrent with the development of mechanical hypersensitivity that was prevented by macrophages depletion or CXCL11 blockade. Finally, myostatin inhibition during established OA, resolved pain and F4/80+iNOS+ macrophage accumulation in the DRG. In conclusion, DRG macrophages maintain OA pain, but are not required for the induction of OA pain. Myostatin is a key ligand in neuro-immune communication that drives the persistence of pain in OA through nervous tissue macrophages and represent a novel therapeutic target for the treatment of OA pain.

Sensitivity analyses of probabilistic and deterministic DTI tractography methodologies for studying arm muscle architecture.

PURPOSE: To determine the sensitivity profiles of probabilistic and deterministic DTI tractography methods in estimating geometric properties in arm muscle anatomy. METHODS: Spin-echo diffusion-weighted MR images were acquired in the dominant arm of 10 participants. Both deterministic and probabilistic tractography were performed in two different muscle architectures of the parallel-structured biceps brachii (and the pennate-structured flexor carpi ulnaris. Muscle fascicle geometry estimates and number of fascicles were evaluated with respect to tractography turning angle, polynomial fitting order, and SNR. The DTI tractography estimated fascicle lengths were compared with measurements obtained from conventional cadaveric dissection and ultrasound modalities. RESULTS: The probabilistic method generally estimated fascicle lengths closer to ranges reported by conventional methods than the deterministic method, most evident in the biceps brachii (p > 0.05), consisting of longer, arc-like fascicles. For both methods, a wide turning angle (50º-90°) generated fascicle lengths that were in close agreement with conventional methods, most evident in the flexor carpi ulnaris (p > 0.05), consisting of shorter, feather-like fascicles. The probabilistic approach produced at least two times more fascicles than the deterministic approach. For both approaches, second-order fitting yielded about double the complete tracts as third-order fitting. In both muscles, as SNR decreased, deterministic tractography produced less fascicles but consistent geometry (p > 0.05), whereas probabilistic tractography produced a consistent number but altered geometry of fascicles (p < 0.001). CONCLUSION: Findings from this study provide best practice recommendations for implementing DTI tractography in skeletal muscle and will inform future in vivo studies of healthy and pathological muscle structure.

Selective chronic recording in small nerve fascicles of sciatic nerve with carbon nanotube yarns in rats.

Objective. The primary challenge faced in the field of neural rehabilitation engineering is the limited advancement in nerve interface technology, which currently fails to match the mechanical properties of small-diameter nerve fascicles. Novel developments are necessary to enable long-term, chronic recording from a multitude of small fascicles, allowing for the recovery of motor intent and sensory signals.Approach. In this study, we analyze the chronic recording capabilities of carbon nanotube yarn electrodes in the peripheral somatic nervous system. The electrodes were surgically implanted in the sciatic nerve's three individual fascicles in rats, enabling the recording of neural activity during gait. Signal-to-noise ratio (SNR) and information theory were employed to analyze the data, demonstrating the superior recording capabilities of the electrodes. Flat interface nerve electrode and thin-film longitudinal intrafascicular electrode electrodes were used as a references to assess the results from SNR and information theory analysis.Main results. The electrodes exhibited the ability to record chronic signals with SNRs reaching as high as 15 dB, providing 12 bits of information for the sciatic nerve, a significant improvement over previous methods. Furthermore, the study revealed that the SNR and information content of the neural signals remained consistent over a period of 12 weeks across three different fascicles, indicating the stability of the interface. The signals recorded from these electrodes were also analyzed for selectivity using information theory metrics, which showed an information sharing of approximately 1.4 bits across the fascicles.Significance. The ability to safely and reliably record from multiple fascicles of different nerves simultaneously over extended periods of time holds substantial implications for the field of neural and rehabilitation engineering. This advancement addresses the limitation of current nerve interface technologies and opens up new possibilities for enhancing neural rehabilitation and control.