Nerve Physiology Research Articles

Microglial and Macrophage Plasticity and Regional Cerebral Blood Flow in the Prenatal Brain and Gut Under Vagus Nerve Stimulation.

An intricate relationship exists between the vagus nerve and systemic immune cell regulation, specifically during fetal development. Little is known about the connection between the vagus nerve and the brain's regional circulatory control. In this chapter, we present a methodology for studying the impact of vagus nerve signaling on these connections in the developing fetus using the sheep model for human fetal physiology. First, we present the protocol to study the connection between the vagus nerve physiology and the regional cerebral blood flow (rCBF). Next, we detail the protocol for measuring how vagal signaling alters microglial cell plasticity in gut and brain. In previous work, our team showed that vagotomy results in amplified redistribution of rCBF toward subcortical structures in the fetal brain. Conversely, efferent VNS reduces rCBF to cortical structures while afferent VNS diminishes the rise of rCBF to subcortical structures (independent of cortical rCBF) when compared to controls in the fetal brain. Additionally, our team showed that Iba-1 expression, a marker for microglial cellular signaling activation, rises in a dose-dependent relationship with systemic inflammatory activation in the setting of vagotomy. The findings support existing preclinical and clinical evidence in adult human physiology that vagotomy is neuroprotective for neurodegenerative diseases such as Parkinson's likely via a glial cell-mediated mechanism. Vagus nerve stimulation (VNS) has also been shown to alter rCBF patterns in adults with treatment-resistant depression, underscoring the importance of further investigation of the relationship between the vagus nerve and rCBF as early as in utero. Together, the body of evidence emphasizes that the vagal pathway is an important player in the programming of microglial cell phenotypes within the developing brain. Further study is needed to better understand the significance of these relationships for the development and treatment of early susceptibility to neuroinflammatory and neurodegenerative disorders in later life. Therefore, we present a methodology for assessing rCBF and morphometric features of microglial and macrophage cell activation to allow future teams to expand on the existing body of work and further examine these relationships at a cellular and systems' levels.

Enhancing the understanding of abstract neurophysiology concepts by first-year students at the University of La Réunion.

Teaching physiology can be challenging as students are initially required to understand basic and abstract concepts. Thus students typically view physiology as a "difficult" subject and place an emphasis on rote learning and memorization. Here, we attempted to address this knowledge gap by introducing a pedagogical intervention into the neurophysiology lesson plan of first-year medical and health physiology students at the University of La Réunion. This intervention aimed to better link abstract concepts (e.g., saltatory conduction) and a pathological disorder (multiple sclerosis), together with a discussion of a specific therapeutic intervention (fampridine). Students were required to complete readings (focused on neurophysiology aspects) and two online quizzes before two scheduled in-person lectures. They could also pose questions on a dedicated online forum. Thereafter, the in-person lectures discussed questions posted on the online forum, provided feedback on poorly answered questions (from the online quizzes), and dealt with questions posed by students attending classes. Student feedback regarding the pedagogic intervention was assessed by an anonymous online survey. This survey revealed that the pedagogical intervention was positively received. For example, 94% of respondents agreed the course was well developed, while 80% indicated that the pedagogical intervention was beneficial in terms of their understanding of basic and abstract neurophysiology concepts. Together, this pedagogical intervention was enthusiastically received by the students who better understood how basic nerve physiology concepts fit into the broader context and that such an understanding can result in the development and the roll-out of unique therapeutic interventions for multiple sclerosis.NEW & NOTEWORTHY First-year physiology students can find the subject challenging, struggling to understand abstract concepts without any context. To address this, we introduced a pedagogical intervention for first-year medical and health physiology students that aimed to link abstract concepts and a pathological disorder, together with a discussion of a specific therapeutic intervention. This pedagogical intervention was well received by first-year physiology students who better understood how basic nerve physiology concepts can be applied within the clinical setting.

The relationship and interdependence of auditory thresholds, proposed behavioural measures of hidden hearing loss, and physiological measures of auditory function

Objectives Standard diagnostic measures focus on threshold elevation but hearing concerns may occur independently of threshold elevation – referred to as “hidden hearing loss” (HHL). A deeper understanding of HHL requires measurements that locate dysfunction along the auditory pathway. This study aimed to describe the relationship and interdependence between certain behavioural and physiological measures of auditory function that are thought to be indicative of HHL. Design Data were collected on a battery of behavioural and physiological measures of hearing. Threshold-dependent variance was removed from each measure prior to generating a multiple regression model of the behavioural measures using the physiological measures. Study Sample 224 adults in the United States with audiometric thresholds ≤65 dB HL. Results Thresholds accounted for between 21 and 60% of the variance in our behavioural measures and 5–51% in our physiological measures of hearing. There was no evidence that the behavioural measures of hearing could be predicted by the selected physiological measures. Conclusions Several proposed behavioural measures for HHL: thresholds-in-noise, frequency-modulation detection, and speech recognition in difficult listening conditions, are influenced by hearing sensitivity and are not predicted by outer hair cell or auditory nerve physiology. Therefore, these measures may not be able to assess threshold-independent hearing disorders.

Dynamic three-dimensional coculture model: The future of tissue engineering applied to the peripheral nervous system

Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, in vitro models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an in vitro coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.

Enhancing Medical Education through the "Distribute, Discuss, and Develop" Method: A Comparative Study of Small-Group Discussions.

Background Small-group discussions (SGDs) are pivotal in medical education, facilitating the development of critical thinking, communication skills, and teamwork. However, traditional SGDs face challenges such as scalability and maintaining student engagement. This study aims to evaluate the "Distribute, Discuss, and Develop" (3D) method for enhancing learning outcomes in medical education. Methods A single-blinded interventional study was conducted with 125 first-year Bachelor of Medicine and Bachelor of Surgery students, who were divided into intervention and control groups through random assignment. The intervention group employed the 3D method across two thematic units: hematology and muscle nerve physiology. The study assessed learning outcomes using pre- and posttests, class-average normalized gain ("g"), and feedback questionnaires to capture student perceptions of interaction, communication enhancement, and session summarization. Results The intervention group showed significantly improved learning outcomes in both thematic units, with larger effect sizes (hematology: 1.55; muscle nerve physiology: 1.4) compared to the control group. The normalized gain "g" indicated a medium effectiveness level for the intervention group in both themes, suggesting enhanced learning. Feedback questionnaires revealed higher satisfaction levels within the intervention group regarding interaction, communication skills, and session summarization. Conclusions The 3D method addresses the challenges faced by traditional SGDs, providing a scalable and engaging approach to medical education. By fostering more effective student-centered learning, the method enhances the comprehension of complex physiological concepts and improves communication skills. The 3Dmethod significantly improves learning outcomes, interaction, and communication skills in medical education. This innovative approach to SGDs offers a promising strategy for enhancing the educational experience in medical schools, supporting the development of more articulate and professionally competent medical graduates.

Perioperative neuropathic and positional problems: literature review

At present, an increasing number of specialists prefer the fast-track surgery concept. One of the significant perioperative complications that can affect the rate and quality of postoperative rehabilitation is the development of neuropathy, which can be the result of improper patient positioning on the operating table, and direct intraoperative damage to the nerve / trunk / plexus. Physical (mechanical compression, stretching, and partial / complete intersection of the nerve with a needle, scalpel, or electrode) and chemical (toxicity of local anesthetics and chemically active liquid effects) mechanisms for neuropathy formation can be described. To prevent the development of a neurological deficit, both the anesthesiologist and surgeon must take all the necessary measures to prevent neuropathies and begin appropriate treatment as soon as possible in the case of its occurrence. This article discusses the anatomy, physiology, and pathophysiology of the peripheral nerve, mechanisms of compression-ischemic neuropathy formation, and perioperative positional problems. Existing recommendations for the treatment of peripheral neuropathic were assessed and proposed for use not only with conservative therapy methods but also with interventional methods for the treatment of established perioperative neurological complications. A summary table of the possible clinical manifestations of postoperative neuropathic is presented.

Neuroinflammation: The missing link between pain and immunity

The density of corneal nerves in the cornea is the highest of the entire body. Most ocular surface diseases/injuries affect corneal neurons and are followed by a process named neurogenic inflammation, which eventually leads to pain, activation and recruitment of leukocytes and neoangiogenesis. On the other hand, leukocytes affect nerve physiology by secreting pro‐inflammatory cytokines and neuropeptides. The clinical outcome of the neuroinflammatory process is two‐faced. While immune activation is beneficial to prevent/control infections and ensure prompt wound healing, a prolonged and/or excessive neuroinflammatory response can have catastrophic consequences on corneal integrity and vision, or induce chronic pain. Clearly, a better understanding of these complex processes can have a deep impact on the treatment of highly prevalent ocular disorders, such as dry eye or infectious keratitis.

"Knowing It Before Blocking It," the ABCD of the Peripheral Nerves: Part A (Nerve Anatomy and Physiology).

Regional anesthesia (RA) is an interplay between the local anesthetic (LA) solution and the neural structures, resulting in nerve conduction blockade. For that, it is necessary to understand which hurdles the LA has to overcome and which components of the nerves are involved. Background knowledge of the neural and non-neural components of the nerve helps locate the safest area for LA deposition. In addition, knowledge of nerve physiology and the conduction process helps to understand the patterns of block onset, involved fibers, and block regression. Neural connective tissue protects the nerve on the one hand and influences the overall effect of the blockade and the occurrence of nerve injuries on the other. The arrangement of the nerve fibers explains the science behind the differential blockage after LA deposition. This article describes the important aspects of nerve anatomy (nerve formation and composition) and nerve physiology (impulse generation and propagation). It also provides insight into the physiological processes involved when a damaged neural structure leads to potential clinical symptoms. It will help readers sharpen their skills and knowledge to execute safe RA without damaging any vital structures in the nerve.

A Novel ENU-Induced Mfn2 Mutation Causes Motor Deficits in Mice without Causing Peripheral Neuropathy.

Mitochondrial fission and fusion are required for maintaining functional mitochondria. The mitofusins (MFN1 and MFN2) are known for their roles in mediating mitochondrial fusion. Recently, MFN2 has been implicated in other important cellular functions, such as mitophagy, mitochondrial motility, and coordinating endoplasmic reticulum-mitochondria communication. In humans, over 100 MFN2 mutations are associated with a form of inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Here we describe an ENU-induced mutant mouse line with a recessive neuromuscular phenotype. Behavioral screening showed progressive weight loss and rapid deterioration of motor function beginning at 8 weeks. Mapping and sequencing revealed a missense mutation in exon 18 of Mfn2 (T1928C; Leu643Pro), within the transmembrane domain. Compared to wild-type and heterozygous littermates, Mfn2L643P/L643P mice exhibited diminished rotarod performance and decreases in activity in the open field test, muscular endurance, mean mitochondrial diameter, sensory tests, mitochondrial DNA content, and MFN2 protein levels. However, tests of peripheral nerve physiology and histology were largely normal. Mutant leg bones had reduced cortical bone thickness and bone area fraction. Together, our data indicate that Mfn2L643P causes a recessive motor phenotype with mild bone and mitochondrial defects in mice. Lack of apparent nerve pathology notwithstanding, this is the first reported mouse model with a mutation in the transmembrane domain of the protein, which may be valuable for researchers studying MFN2 biology.

Visualization of axonal and volume currents in median nerve compound action potential using magnetoneurography

ObjectiveReconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials. MethodsThe median nerves of both upper arms of five healthy individuals were investigated. The propagating magnetic field of the action potential was recorded using magnetoneurography, reconstructed into a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes. ResultsReconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conductor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approximately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones. ConclusionsMagnetoneurography allows the visualization and quantitative evaluation of action currents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings. SignificanceMagnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.

Hepatic Innervations and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

Understanding the physiology of the human vagus nerve from intraneural microelectrode recordings

Understanding the physiology of the human vagus nerve from intraneural microelectrode recordings

Cisternal, Falciform, and Optic Canal Decompression Influencing Optic Nerve Biomechanics: A Microsurgical Anatomic Study.

Questions remain regarding optic nerve (ON) physiology, mechanical compliance, and microvasculature, particularly surgical outcomes and atypical visual field defects associated with sellar/parasellar pathology (eg, tumors and aneurysms). To study the microsurgical/histological anatomy of each ON segment and corresponding microvasculature, calculate area of optic-carotid space at each decompression stage, and measure ON tension before/after compression. Five cadaveric heads (10 sides) underwent sequential dissection: (1) intradural (arachnoidal) ON dissection; (2) falciform ligament opening; (3) anterior clinoidectomy, optic canal decompression, and ON sheath release. At each step, we pulled the nerve superiorly/laterally with a force meter and measured maximal mobility/mechanical tension in each position. Cisternal ON microvasculature was more superficial and less dense vs the orbital segment. ON tension was significantly lower with higher mobility when manipulated superiorly vs lateromedially. Optic-carotid space significantly increased in size at each decompression stage and with ON mobilization both superiorly and laterally, but the increase was statistically significant in favor of upward mobilization. At decompression step, upward pull provided more space with less tension vs side pull. For upward pull, each step of decompression provided added space as did side pull. Opening the optic canal, falciform ligament, and arachnoid membrane decompresses the ON for safer manipulation and provided a wider optic-carotid surgical corridor to access sellar/parasellar pathology. When tailoring decompression, the ON should be manipulated superiorly rather than lateromedially, which may guide surgical technique, help prevent intraoperative visual deterioration, facilitate postoperative visual improvement, and help understand preoperative visual field deficits based on mechanical factors.

Physiology of the Vagus Nerve: Basic Medical Research from the Past to the Present

The vagus nerve, which is the 10th cranial nerve, exits from the medulla and distributes widely to the visceral organs. Although it contains the motor, somatic, and sympathetic nerves, the main component is the parasympathetic nerve, which acts as the core of homeostasis. The vagal efferent regulates the cardiac muscle, striated muscle and glands, while the vagal afferent sends the information from the visceral organs to the brain. The vagus nerve is also responsible for the gut-brain axis.

Standard-Setting of Multidisciplinary Objective Structured Practical Examination.

PurposeThe present work applies the standard-setting in the multidisciplinary Objective Structured Practical Examination (OSPE) of the MusculoSkeletal and Integument systems (MSK) module using Modified Ebel’s method to differentiate the competent students from the non-competent ones.Materials and methodsOne hundred fifty-six students participated in the multidisciplinary OSPE. The MSK-OSPE consists of mid-module and final. According to the blueprint of the OSPE, the mid-module OSPE tested the knowledge and skills of the upper limb, and the final OSPE verified the knowledge and skills of the lower limb. Modified Ebel’s method was used to identify the Minimum Pass Level (MPL) in each station and the whole exam accordingly.ResultsFifty-seven percent (57%) of the students passed both exams, while 25.6% did not pass the mid-module exam and 31.4% did not pass the final exam, 17.9% did not pass both exams and 25% did not pass one exam. The MPL for most of the stations in both exams using modified Ebel’s method of the standard-setting was more than 50% which is the conventional pass mark. However, the MPL for stations 4, and 6 in the mid-module exam (ulna and arteries of the upper limb) and stations 7, 9, and 14 (muscles of the lower limb, anatomy of ankle joint, physiology of nerve) was < 50%. While the total pass mark of the mid-module OSPE was 66% and the pass mark for the final OSPE was 60%ConclusionThe minimal pass level (MPL) in mid module and final OSPE were 66% and 60% respectively which are more than the conventional cut off point (50%) that indicating that the standard-setting was effective in identifying poor performers who cannot be identified by the conventional method that led to enhance the quality of OSPE as an assessment tool. Moreover, students developed the skills to deal with standardized patients in clinical stations. However, some defects and areas of improvement were identified in some physiological and anatomical stations. The organizing committee recommended identifying the poor performers and conducting extra-tutorial sessions on the defective topics.

The Quantum Motion of the Nerve with a Local Defect

We consider the nerve as the elastic string, the left end of which is fixed at the beginning of the coordinate system, the right end is fixed at point l and mass m is fixed between the ends of the string. We determine the classical and the quantum vibration of such system. The quantum motion is obtained by the so-called non-conventional oscillator quantization method by author. The proposed model can be also related in the modified form to the problem of the Mossbauer effect, being the recoilless nuclear resonance fluorescence, which is the resonant and recoil-free emission and absorption of gamma radiation by atomic nuclei bound in a solid. (Mossbauer,1958). It is not excluded that our oscillator quantization of the string can be extended to generate the new way of the string theory of matter and physiology of nerves.

Pathophysiology of Airway Afferent Nerves

Abstract Vagal afferent nerves provide an airway defense mechanism which is ensured by their activation. These nerves can be activated mechanically mainly through mechanosensitive Aβ fibers which are divided into slowly adapting (SARs) and rapidly adapting stretch receptors (RARs). Chemical activation is provided by an interaction of chemical substances with specific receptors. C-fibers are highly sensitive to a direct chemical stimulation accomplished by an activation of ligand-gated ion channels. According to the large influence and mechanisms of vagal afferent nerves, there is a probability that an inappropriate activity of these nerves can cause the symptoms of the respiratory diseases, e.g. cough, dyspnoea, or airway hyperreactivity. The aim of this review is to summarize the physiology of airway afferent nerves and point out the role of vagal sensory nerves dysfunction in the pathogenesis of some respiratory diseases. The understanding of its mechanism could lead to new therapeutic strategies in patients with airway-related pathology.

The Anatomy, Physiology, and Histology of Optic Nerve

The optic nerve (Nervus opticus) is the second of the 12 cranial nerves and is considered to be a part of the central nervous system. It carries visual information from the neurosensory retina to the occipital cortex. The nerve consists of the axons of retinal ganglion cells (RGCs). These axons extend in an organized pattern from the RGC soma to the lateral geniculate nucleus where the neuron's synapse. The nerve is subdivided into fascicles by connective tissue and glial septa, and it is surrounded by cerebrospinal fluid. The optic nerve has intraocular, intraorbital, intracanalicular, and intracranial parts and a length of approximately 50 mm. The central retinal artery, the Zinn-Haller circle formed by the short posterior ciliary artery extensions, and pial vessels take part in the blood supply of the nerve.

Functional reconstruction of lower extremity nerve injuries

Peripheral nerve injuries (PNI) in the lower extremity are an uncommon but highly morbid condition. Recent advances in our understanding of nerve physiology and microsurgical techniques have inspired renewed faith in nerve surgery and sparked a creative renaissance in the tools, approaches, and reconstructive schemas available to surgeons in the management of lower extremity PNIs. In this article, we review the literature and provide a principles-based approach for the surgical management of lower extremity PNIs with an emphasis on techniques for functional reconstruction after complete nerve injury. General principles in management include early diagnosis with electrodiagnostics and imaging, early surgical exploration, and opting for nerve and tendon transfers when primary reconstruction of the injured nerve is unfavorable (e.g., delayed reconstruction, unavailability of proximal or distal nerve stumps, or long regenerative distance). The goal of functional reconstruction should be to restore independent gait, so understanding the roles of major neuromuscular units during the gait cycle informs the selection of donor nerves and tendons for transfer. Based on these principles and literature to date, specific algorithms for surgical management are presented for femoral, sciatic, tibial, and common peroneal nerves. We recognize limitations of the current literature, namely the predominance of case series evidence, and call for the accrual of more patient data in surgical management of PNIs.

New Stimulation Device to Drive Multiple Transverse Intrafascicular Electrodes and Achieve Highly Selective and Rich Neural Responses.

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator—called STIMEP—and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes.