Nerve Endings Research Articles

Anatomical characteristics of the phrenic nerve and the spontaneous conduction block between the right atrium and the superior vena cava

Abstract Introduction Although the superior vena cava isolation (SVCI) with minimal radiofrequency application using a spontaneous right atrium – superior vena cava (RA-SVC) conduction block has been reported, the anatomical characteristics of the spontaneous RA-SVC conduction block is not clear. Purpose The aim of this study to evaluate the anatomical relationship between the spontaneous RA-SVC conduction block and the phrenic nerve (PN). Methods This study consisted of 73 patients who attempted to undergo SVCI using a RA-SVC conduction block. The RA-SVC conduction block was visualized using the extended early meets late tool with the CARTO3 system. We set the first lower threshold at 1800/total local activation time to optimize the visualization of spontaneous RA-SVC conduction block. If the SVC was not isolated by ablation to the gap of the visualized conduction block line, the lower threshold was increased by 5%, and the new gap was ablated each time. The course of the right PN was detected by pacing with 20 mA /2 ms. The RA-SVC conduction block and the course of the PN were measured with reference to the height of the left atrial roof. The extend of the RA-SVC conduction block and PN were measured in angles with respect to the ventral side (Figure 1). These anatomical parameters were compared between the RA-SVC block line and the PN. Results Sixty-one patients (83.6%) had spontaneous RA-SVC conduction block, and the remaining 12 patients (16.4%) did not. Anatomical characteristics were evaluated in 61 patients with spontaneous RA-SVC conduction block. Compared with the course of the PN, RA-SVC conduction block extended more posteriorly (110 degrees vs 128 degrees, P = 0.013) and more caudally (9.5 mm vs 16.1 mm, P<0.0001) (Figure 2). In the patients who underwent SVCI using a RA-SVC conduction block, any patients did not undergo radiofrequency application on the course of the PN. Conclusion Since the caudal end of the RA-SVC conduction block is posterior to the caudal end of the phrenic nerve, SVCI using the RA-SVC conduction block may be able to avoid ablation near the PN.Figure1Figure2

Electrophysiological Signal Validation of Regenerative Peripheral Nerve Interface at Nerve Ending: A Preliminary Rat Model Experiment.

As the number of extremity amputations continues to rise, so does the demand for prosthetics. Emphasizing the importance of a nerve interface that effectively amplifies and transmits physiological signals through peripheral nerve surgery is crucial for achieving intuitive control. The regenerative peripheral nerve interface (RPNI) is recognized for its potential to provide this technical support. Through animal experiment, we aimed to confirm the actual occurrence of signal amplification. Rats were divided into three experimental groups: control, common peroneal nerve transection, and RPNI. Nerve surgeries were performed for each group, and electromyography (EMG) and nerve conduction studies (NCS) were conducted at the initial surgery, as well as at 2, 4, and 8 weeks postoperatively. All implemented RPNIs exhibited viability and displayed adequate vascularity with the proper color. Clear differences in latency and amplitude were observed before and after 8 weeks of surgery in all groups (p < 0.05). Notably, the RPNI group demonstrated a significantly increased amplitude compared with the control group after 8 weeks (p = 0.031). Latency increased in all groups 8 weeks after surgery. The RPNI group exhibited relatively clear signs of denervation with abnormal spontaneous activities (ASAs) during EMG. This study is one of few preclinical studies that demonstrate the electrophysiological effects of RPNI and validate the neural signals. It serves as a foundational step for future research in human-machine interaction and nerve interfaces.

Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system.

Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.

Impact of Neurostimulation, Immunomodulation, Topical Medication Application, and Surgical Reconstruction on Corneal Nerve Function and Regeneration.

The corneal epithelium, supplied by thousands of nerve endings, plays a substantial role in absorbing and distributing nutrients along the ocular surface. Many studies have explored the influence of various modalities in regulating tear production to manage corneal disorders and dry eye disease. These findings have highlighted the advantages of enhancing corneal nerve function and regeneration through neurostimulation, neural signaling, immunomodulation, topical medication application, and surgical reconstruction. The purpose of this narrative review article was to provide an overview of the current state of knowledge on this topic based on a PubMed database literature search for relevant animal and human studies investigating the modification of the trigeminal pathway to restore corneal nerve function and improve overall ocular health. Further investigation into this area of research is important to help guide new therapeutic targets for the prevention and development of treatments of corneal degeneration.

Effect of Yiqi Huoxue Decoction on Neurological Function for Cervical Spinal Cord Injury

Cervical spinal cord injury (CSCI) can lead to neurological dysfunction, such as limb numbness, muscle stiffness, and motor disorders. Although early decompression surgery has demonstrated efficacy in alleviating symptoms for patients with CSCI, there are still some limitations in the recovery of motor function. It has been reported that traditional Chinese medicine (TCM) has advantages in the treatment of CSCI due to its safety and efficacy and its ability to modulate the immune system and promote neuroregeneration. In this study, we investigate the clinical efficacy of combining Yiqi Huoxue Decoction with acupoint massage therapy in patients with CSCI after decompression and fixation surgery. A total of 140 patients who were first diagnosed with CSCI at our hospital and underwent early decompression and internal fixation surgery from October 2022 to June 2023 were included in this study. They were divided into two groups: Group A (n = 70) received conventional Western medicine treatment, and Group B (n = 70) received Yiqi Huoxue Decoction and acupoint massage therapy. We observed significant improvements in the American Spinal Injury Association scores after the combined treatment. Moreover, the levels of neuron-specific enolase decreased, while the levels of nerve growth factor and insulin-like growth factor-1 increased. Additionally, the levels of CD3+, CD4+, and CD8+ T cells exhibited a notable decrease. Furthermore, acupoint massage was found to stimulate nerve endings, thereby promoting nerve regeneration and repair. In summary, this combined treatment effectively improves the neurological function of patients with CSCI.

Fabrication of Anatomically Equivalent Pectin-Based Multifilament Nerve Conduits.

Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 μm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

A Quadruple Gene-Deleted Live BoHV-1 Subunit RVFV Vaccine Vector Reactivates from Latency and Replicates in the TG Neurons of Calves but Is Not Transported to and Shed from Nasal Mucosa.

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.

Cajal's contributions to vestibular research.

The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or the direction followed by nerve impulses (the principle of dynamic polarization), he described numerous details regarding the organization of the different structures of the nervous system. This task was compiled in his magnum opus, "Textura del Sistema Nervioso del Hombre y los Vertebrados," first published in Spanish between 1899 and 1904, and later revised and updated in French as "Histologie du système nerveux de l'homme et des vertébrés" between 1909 and 1911 for wider distribution among the international scientific community. Some of Cajal's findings are fundamental to our understanding of the anatomy and histology of the vestibular system. He depicted the nerve endings in the sensory epithelia, the structure of the vestibular nerve and Scarpa ganglion, afferent vestibular fibers, vestibular nuclei, lateral vestibulospinal tract, vestibulocerebellar connections, and the fine structure of the cerebellum. However, most of these pioneering descriptions were published years earlier in Spanish journals with limited circulation. Our study aimed to gather Cajal's findings on the vestibular system and identify his original publications. After this endeavor, we claim a place for Cajal among the founders of anatomy and histology of the vestibular system.

Tensile Strength of Nerve Bridging Models Using Collagen Nerve Conduits.

In the treatment of peripheral nerve injuries with nerve defects, second-generation collagen-based conduits, such as Renerve® (Nipro, Osaka, Japan), have shown the potential for promoting nerve regeneration. However, there is concern related to the weak material properties. No previous studies have addressed the strength of the bridging model using collagen conduits. This study aimed to investigate the tensile strength and failure patterns in nerve defect models bridged with Renerve® conduits through biomechanical research. Using fresh chicken sciatic nerves, we examined the maximum failure load of four groups: bridging models using Renerve® with one suture (group A), with two sutures (group B), with three sutures (group C), and end-to-end neurorrhaphy models with two sutures (group N). Each group had eight specimens. We also evaluated failure patterns of the specimens. Group N showed a significantly higher maximum failure load (0.96 ± 0.13 N) compared to groups A (0.23 ± 0.06 N, p < 0.0001), B (0.29 ± 0.05 N, p < 0.0001), and C (0.40 ± 0.10 N, p < 0.0001). Regarding failure patterns, all specimens in group A showed nerve-end dislocation from the conduit. Two specimens in group B and three specimens in group C failed due to circumferential cracks in the conduit. Six specimens in group B and five specimens in group C exhibited cutting out of sutures from the conduit. This study suggests that the number of sutures in synthetic collagen nerve conduits has little effect on the maximum failure load. To take advantage of its biomaterial benefits, a period of postoperative range of motion restriction may be required.

Endocytosis of Synaptic Vesicle in Motor Nerve Endings of FUS Transgenic Mice with a Model of Amyotrophic Lateral Sclerosis.

In experiments on the motor nerve endings of the diaphragm of transgenic FUS mice with a model of amyotrophic lateral sclerosis at the pre-symptomatic stage of the disease, the processes of transmitter release and endocytosis of synaptic vesicles were studied. In FUS mice, the intensity of transmitter release during high-frequency stimulation of the motor nerve (50 imp/sec) was lowered. At the same duration of stimulation, the loading of fluorescent dye FM1-43 was lower in FUS mice. However, at the time of stimulation, during which an equal number of quanta are released in wild-type and FUS mice, no differences in the intensity of dye loading were found. Thus, endocytosis is not the key factor in the mechanism of synaptic dysfunction in FUS mice at the pre-symptomatic stage.

Unveiling Niaprazine's Potential: Behavioral Insights into a Re-Emerging Anxiolytic Agent.

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety. Despite its potential benefits, the behavioral effects of NIA have not been thoroughly investigated. This study aimed to examine NIA's potential as an anti-anxiety and anti-stress agent. After administering either vehicle or NIA in their drinking water to mice for 14 days, we conducted behavioral analyses using the Marble Burying Test and the Elevated Plus Maze test. NIA-treated mice spend more time in the open arms and bury fewer marbles. Moreover, a stability study confirmed the linear relationship between NIA concentration and its response across concentrations encompassing the NIA mother solution and the NIA solutions administered to mice. Also, a preliminary synaptic toxicity analysis showed no direct damage to cortical nerve endings. Here, we show that NIA can modulate anxiety-related behaviors without significantly impacting exploratory activity or adverse effects. Our work describes new findings that contribute to the research on safer and more tolerable anxiety management options.

Collagen protein-chitosan nerve conduits with neuroepithelial stem cells promote peripheral nerve regeneration

The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients’ quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.

Biomechanical Evaluation of an Atraumatic Polymer-assisted Peripheral Nerve Repair System Compared with Conventional Neurorrhaphy Techniques.

Microsuturing, the gold standard for peripheral nerve repair, can create tension and damage at the repair site, potentially impacting regeneration and causing neuroma formation. A sutureless and atraumatic polymer-assisted system was developed to address this challenge and support peripheral nerve repair. The system is based on a biocompatible and biodegradable biosynthetic polymer and consists of a coaptation chamber and a light-activated polymer for securing to the nerve. In this study, we compare the system's biomechanical performance and mechanism of action to microsutures and fibrin repairs. The system's fixation force was compared with microsutures and fibrin glue, and evaluated across various nerve diameters through tensile testing. Tension and tissue morphology at the repair site were assessed using finite element modeling and scanning electron microscopy. The fixation force of the polymer-assisted repair was equivalent to microsutures and superior to fibrin glue. This force increased linearly with nerve diameter, highlighting the correlation between polymer surface contact area and performance. Finite element modeling analysis showed stress concentration at the repair site for microsuture repairs, whereas the polymer-assisted repair dissipated stress along the nerve, away from the repair site. Morphological analysis revealed nerve alignment with no tissue trauma for the polymer-assisted repair, unlike microsutures. The mechanical performance of the polymer-assisted coaptation system is suitable for peripheral nerve repair. The achieved fixation forces are equivalent to those of microsutures and superior to fibrin glue, minimizing stress concentration at the repair site and avoiding trauma to the severed nerve ends.

Cartilage Integrity: A Review of Mechanical and Frictional Properties and Repair Approaches in Osteoarthritis.

Osteoarthritis (OA) is one of the most common causes of disability around the globe, especially in aging populations. The main symptoms of OA are pain and loss of motion and function of the affected joint. Hyaline cartilage has limited ability for regeneration due to its avascularity, lack of nerve endings, and very slow metabolism. Total joint replacement (TJR) has to date been used as the treatment of end-stage disease. Various joint-sparing alternatives, including conservative and surgical treatment, have been proposed in the literature; however, no treatment to date has been fully successful in restoring hyaline cartilage. The mechanical and frictional properties of the cartilage are of paramount importance in terms of cartilage resistance to continuous loading. OA causes numerous changes in the macro- and microstructure of cartilage, affecting its mechanical properties. Increased friction and reduced load-bearing capability of the cartilage accelerate further degradation of tissue by exerting increased loads on the healthy surrounding tissues. Cartilage repair techniques aim to restore function and reduce pain in the affected joint. Numerous studies have investigated the biological aspects of OA progression and cartilage repair techniques. However, the mechanical properties of cartilage repair techniques are of vital importance and must be addressed too. This review, therefore, addresses the mechanical and frictional properties of articular cartilage and its changes during OA, and it summarizes the mechanical outcomes of cartilage repair techniques.

Activation of nociception-sensitive ionotropic glutamate receptor-expressing rostroventrolateral medulla neurons by stimulation of cardiac afferents in rats.

Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non-barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABAA agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5- phosphonopentanoic acid (AP5), or non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Baroreceptor loading-induced inhibition of barosensitive activity attenuated the bradykinin-induced RSNA response (93 ± 14% increase) and tachycardia (18 ± 3 bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6 ± 4.2% from baseline, 0.49 ± 0.38 μV*s), surprisingly, it did not abolish the tachycardia (27 ± 4 bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception-sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM.

Neuroscience of cancer: Research progress and emerging of the field.

Cancer cells immediately expand and penetrate adjoining tissues, as opposed to metastasis, that is the spread of cancer cells through the circulatory or lymphatic systems to more distant places via the invasion process. We found that a lack of studies discussed tumor development with the nervous system, by the aspects of cancer-tissue invasion (biological) and chemical modulation of growth that cascades by releasing neural-related factors from the nerve endings via chemical substances known as neurotransmitters. In this review, we aimed to carefully demonstrate and describe the cancer invasion and interaction with the nervous system, as well asreveal the research progress and the emerging neuroscience of cancer. An initial set of 160 references underwent systematic review and summarization. Through a meticulous screening process, these data were refined, ultimately leading to the inclusion of 98 studies that adhered to predetermined criteria. The outcomes show that one formidable challenge in the realm of cancer lies in its intrinsic heterogeneity and remarkable capacity for rapid adaptation. Despite advancements in genomics and precision medicine, there is still a need to identify new molecular targets. Considering cancer within its molecular and cellular environment, including neural components, is crucial for addressing this challenge. In conclusion, this review provides good referential data for direct, indirect, biological, and chemical interaction for nerve tissue-tumor interaction, suggesting the establishment ofnew therapy techniques and mechanisms by controlling and modifying neuron networks that supply signals to tumors.

Territories of Nerve Endings of the Medial Plantar Nerve within the Abductor Hallucis Muscle: Clinical Implications for Potential Pain Management.

This study aimed to elucidate the intramuscular distribution pattern of the medial plantar nerve and determine its motor nerve ending territories within the abductor hallucis muscle using modified Sihler's staining and external anatomical landmarks. The study included 40 specimens of the abductor hallucis muscle (13 men and seven women) from formalin-fixed (ten cadavers) and fresh cadavers (ten cadavers), with a mean age of 77.6 years. The entry point of the medial plantar nerve into the muscle was examined, followed by Sihler's staining to analyze the intramuscular distribution pattern and motor nerve ending location within the abductor hallucis muscle. Ultrasound- and palpation-guided injections were performed to verify the applicability of motor nerve ending location-based injections. The areas with the highest concentrations of nerve entry points and nerve endings were identified in the central portion of the muscle. Ultrasound- and palpation-guided injections were safely positioned near the densest nerve ending region of the muscle. These detailed anatomical data and injection methods would be beneficial for proceeding with safe and effective injection treatments using various analgesic agents to alleviate abductor hallucis muscle-associated pain disorders.

Nerve entry points in the mimic musculature of the horse head.

Facial expressions are important in pain recognition in horses, but current observation-based pain scales remain subjective. A promising technique to quantitatively measure subtle changes in expression patterns, including changes invisible to the human eye, is surface electromyography (sEMG). To achieve high-quality and reliable sEMG signals, unilateral placement of bipolar electrodes is required in relation to the motor endplates (MEP). We aimed to localize the nerve entry points (NEPs; where the nerve branch first pierced the muscle belly) and the direction of the terminal nerve endings to estimate MEP locations of the innervating nerves in five equine facial muscles involved in pain expression. Three cadaveric Dutch Warmblood horse heads were dissected to identify the NEPs in the musculi caninus, levator anguli oculi medialis, nasolabialis, masseter and zygomaticus. These points were marked with pins and measured in relation to a reference line between two anatomical landmarks near the origin and insertion of the respective muscle. Relative distances were calculated from the most caudally situated landmark. NEPs were located at 33%-38% (caninus), 69%-86% (levator anguli oculi medialis) and 0%-18% (zygomaticus) from the caudal landmark. The nasolabialis showed two innervations zones. Its NEPs were located at 47%-72% (dorsal muscle branch) and 52%-91% (ventral branch). All terminal nerve endings were found to run in rostral direction. The masseter showed numerous NEPs diffusely spread within the muscle belly. Therefore, calculation of relative positions was not performed. These results could form the basis for feasibility studies and standardization of bipolar electrode positioning invivo to measure facial muscle activity patterns in horses.

Abstract Tu047: Carbonic anhydrase inhibitors (CAIs) mitigate cardiac amyloid β pathology, attenuating neuro-signaling adverse remodeling and improving cardiac function in the Tg2676- AD mouse model.

FDA-approved carbonic anhydrase inhibitors (CAIs) have been shown to attenuate Aβ pathology, neurodegeneration, and cerebrovascular dysfunction in models of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), suggesting a key role for CAs as a novel and previously unexplored target for AD therapy. Amyloid-β accumulation severely impairs the cerebral neuro-signaling pathway with a progressive loss in neurotrophic factors (like BDNF), potentially also affecting the cardiac nervous system and culminating in lethal heart dysfunction. Yet, no studies have proposed the use of CAIs for treating and preventing the systemic and cardiac effects of amyloidosis and AD. Here, we explored for the first time, the protective effects of a chronic CAIs therapeutic regimen against cardiac amyloid pathology, neuronal fibers’ loss, and heart neurotrophic dysregulation in Tg2576 mice, a widely used model of AD and cerebral amyloidosis. Cardiac fibrosis enhancement along with progressive Aβ deposition in the heart seriously affected the cardiac neuro-signaling pathway culminating in a robust decline of BDNF expression associated with myocardial adrenergic nerve fibers and regenerated nerve endings impoverishment (stained with TH and GAP-43 respectively) in 13-month-old Tg2576 mice compared to age-matched WT littermates. These degenerative mechanisms severely compromised heart function, evidenced by a decline of both ejection fraction and fraction shortening percentage in Tg2576 animals. Accordingly, we observed that human Aβ40 or Aβ42 oligomers’ treatment drastically reduced BDNF and GAP-43 expression in human neuronal cells and human cardiomyocytes. Notably, long-term CAIs treatment in Tg2576 mice reduced Aβ accumulation in the heart tissue and reverted cardiac neuro-signaling pathway adverse remodeling, thus ameliorating heart function, as evidenced through speckle tracking-based strain echocardiography analysis. These in vivo results were validated by in vitro experiments both in neuronal and cardiac cells. These findings suggest a new beneficial role of CAIs in preventing the Aβ induced cardiovascular remodeling and neuro-signaling deregulation for the first time in the Tg2576 model of AD. Taken together with the positive effects of CAIs on cerebrovascular function and cognition, this study paves the way for future clinical trials aimed at repurposing FDA-approved CAIs to prevent and correct both central and peripheral pathologies induced by AD and amyloidosis.