Efficacy Of Nerve Stimulation Research Articles

A motion intention-based upper limb rehabilitation training system to stimulate motor nerve through virtual reality

Motor rehabilitation strategies for treating motor deficits after stroke are based on the understanding of the neural plasticity. In recent years, various upper limb rehabilitation robots have been proposed for the stroke survivors to provide relearning of motor skills by stimulating the motor nerve. However, several aspects including costing, human–robot interaction, and effective stimulation of motor nerve still remain as major issues. In this article, a new upper limb rehabilitation training system named as motion intention-based virtual reality training system is developed to close the aforementioned issues. The system identifies the user’s motion intention via force sensors mounted on the rehabilitation robot to conduct therapeutic exercises and stimulates the user’s motor nerve by introducing the illusion of immersion in virtual reality environment. The illusion of immersion is developed by creating Virtual Exoskeleton Robot model which is driven by user’s motion intention and reflecting the motion states in real time. The users can be present to the training exercises by themselves and fully engage in the virtual reality environment, so that they can relax, move, and recreate motor neuro-pathways. As preliminary phase, six healthy subjects were invited to participate in experiments. The experimental results showed that the motion intention-based virtual reality training system is effective for the upper limb rehabilitation exoskeleton and the evaluations of the developed system showed a significant reduction of the performance error in the training task.

Excitability and firing behavior of single slow motor axons transmitting natural repetitive firing of human motoneurons.

Excitability of motor axons is critically important for realizing their main function, i.e., transmitting motoneuron firing to muscle fibers. The present study was designed to explore excitability recovery and firing behavior in single slow axons transmitting human motoneuron firing during voluntary muscle contractions. The abductor digiti minimi, flexor carpi ulnaris, and tibialis anterior were investigated during threshold stimulation of corresponding motor nerves. Motor unit (MU) firing index in response to testing volleys evoking M-responses was used as a physiological measure of axonal excitability and its changes throughout a target interspike interval (ISI) were explored. It was shown that axons displayed an early irresponsive period (within the first ~2-5 ms of a target ISI) that was followed by a responsive period (for the next 5-17 ms of the ISI), in which MUs fired axonal doublets, and a later irresponsive period. At the beginning of the responsive period, M-responses showed small latency delays. However, since at that ISI moment, MUs displayed excitability recovery with high firing index, slight latency changes may be considered as a functionally insignificant phenomenon. The duration of axonal doublet ISIs did not depend on motoneuron firing frequencies (range 4.3-14.6 imp/s). The question of whether or not traditionally described axonal recovery excitability cycle is realistic in natural motor control is discussed. In conclusion, the present approach, exploring, for the first time, excitability recovery in single slow axons during motoneuron natural activation, can provide further insight into axonal firing behavior in normal states and diseases.NEW & NOTEWORTHY Excitability of single slow axons was estimated by motor unit firing index in response to motor nerve stimulation, and its changes throughout a target interspike interval were explored during transmitting human motoneuron natural firing. It was found that axons exhibited early irresponsive, responsive, and later irresponsive periods. Findings question whether the traditionally described axonal excitability recovery cycle is realistic in natural motor control.

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis.

Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune-mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies. Together, these data suggest that the ANS may control inflammation in humans. This notion is supported by experimental studies in animal models of RA. We have found that stimulation of the so-called cholinergic anti-inflammatory pathway by efferent electrical vagus nerve stimulation (VNS) or pharmacological activation of the alpha7 subunit of nicotinic acetylcholine receptors (α7nAChR) improves clinical signs and symptoms of arthritis, reduces cytokine production and protects against progressive joint destruction. Conversely, increased arthritis activity was observed in alpha7nAChR knockout mice. These studies together with previous work in animal models of sepsis and other forms of inflammation provided the rationale for an experimental clinical trial in patients with RA. We could for the first time show that an implantable vagus nerve stimulator inhibits peripheral blood cytokine production in humans. VNS significantly inhibited TNF and IL-6 production and improved RA disease severity, even in some patients with therapy-resistant disease. This work strongly supports further studies using a bioelectronic approach to treat RA and other IMIDs.

Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction.

Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats.Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF.Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts.NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents but indirectly activated a subpopulation of second- and higher-order neurons, suggesting that afferent mechanisms and central neuron activation may be responsible for vagus nerve stimulation efficacy.

Transdermal optogenetic peripheral nerve stimulation

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

The assessment of neuromuscular fatigue during 120\xa0min of simulated soccer exercise

PurposeThis investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions.MethodsTen male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response.ResultsAt HT, FT, and ET, reductions in maximal voluntary force (MVC; −11, −20 and −27%, respectively, P ≤ 0.01), potentiated twitch force (−15, −23 and −23%, respectively, P < 0.05), voluntary activation (FT, −15 and ET, −18%, P ≤ 0.01), and voluntary activation measured with TMS (−11, −15 and −17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6–11%; ICC2,1 0.83–0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5–18%; ICC2,1 0.63–0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3–6%; ICC2,1 0.90–0.98).ConclusionSimulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms.

Procedures for Evaluating the Adequacy of Anesthesia.

Assessing adequacy of anesthesia requires evaluation of its components: hypnosis, analgesia, and neuromuscular transmission. In order to do this, many methods have been developed that process signals representing different modalities. Assessment of hypnosis requires cortical measures of the central nervous system (CNS); methods that assess analgesia concentrate on subcortical and spinal levels of the CNS; and neuromuscular transmission is a peripheral phenomenon. This article presents an overview of the current state of methods available for measuring each of these components. We conclude that, whereas important gains have been made in the area of assessment of hypnosis, mainly owing to the advancement of methods using EEG and auditory evoked potentials, and whereas neuromuscular transmission can be objectively monitored using motor nerve stimulation, assessment of analgesia still contains many challenges.

Activity-dependent redistribution of Kv2.1 ion channels on rat spinal motoneurons.

Homeostatic plasticity occurs through diverse cellular and synaptic mechanisms, and extensive investigations over the preceding decade have established Kv2.1 ion channels as key homeostatic regulatory elements in several central neuronal systems. As in these cellular systems, Kv2.1 channels in spinal motoneurons (MNs) localize within large somatic membrane clusters. However, their role in regulating motoneuron activity is not fully established in vivo. We have previously demonstrated marked Kv2.1 channel redistribution in MNs following in vitro glutamate application and in vivo peripheral nerve injury (Romer et al., 2014, Brain Research, 1547:1–15). Here, we extend these findings through the novel use of a fully intact, in vivo rat preparation to show that Kv2.1 ion channels in lumbar MNs rapidly and reversibly redistribute throughout the somatic membrane following 10 min of electrophysiological sensory and/or motor nerve stimulation. These data establish that Kv2.1 channels are remarkably responsive in vivo to electrically evoked and synaptically driven action potentials in MNs, and strongly implicate motoneuron Kv2.1 channels in the rapid homeostatic response to altered neuronal activity.

Endothelial-smooth muscle cell interactions in the regulation of vascular tone in skeletal muscle.

The SMCs of skeletal muscle arterioles are intricately sensitive to changes in membrane potential. Upon increasing luminal pressure, the SMCs depolarize, thereby opening VDCCs, which leads to contraction. Mechanisms that oppose this myogenic tone can involve voltage-dependent and independent dilator pathways, and can be endothelium-dependent or independent. Of particular interest are the pathways leading to hyperpolarization of SMCs, as these can potentially evoke both local and conducted dilation. This review focuses on three agonists that cause local and conducted dilation in skeletal muscle: ACh, ATP, and KCl. The mechanisms for the release of these agonists during motor nerve stimulation and/or hypoxia, and their actions to open either Ca2+ -activated K+ channels (KCa ) or inwardly rectifying K+ channels (KIR ) are described. By causing local and conducted dilation, each agonist has the ability to improve skeletal muscle blood flow during exercise and ischemia.

Hyperthermia and supraspinal fatigue.

Hyperthermia and supraspinal fatigue.

Calcium Transient Registration in Response to Single Stimulation and During Train of Pulses in Mouse Neuromuscular Junction

Calcium (Ca2+) is a key ion involved in transmitter release in chemical synapses. Optical recording of fluorescence changes of Ca2+ indicators is one of the most frequently used methods to measure intracellular Ca2+ dynamics. This technique is based on use of Ca2+-binding fluorescent dyes which change their emission intensity after binding to Ca2+. The most crucial step in this type of experiments is loading of Ca2+ dye. In this paper, we present the method of Ca2+-sensitive dye loading to mammalian nerve endings through the stump of the nerve. We represent Ca2+ transient registered parameters in response to a single motor nerve stimulus. The study of Ca2+ dynamics during high frequency stimulation close to real pattern of synaptic transmission allows us to understand such fundamental process as synaptic plasticity. We describe the results obtained during the registration of Ca2+ transient caused by the rhythmic motor nerve stimulation. Intracellular level of Ca2+ estimated by the amplitude of Ca2+ transient rises with the increase of stimulation frequency. The amplitude of Ca2+ transient decreases after blocking of voltage dependent Ca2+ channels by cadmium. The obtained data showed that detected increase of fluorescence intensity is induced by Ca2+ influx through the voltage-gated Ca2+ channels to the nerve ending during an action potential. This dye-loading method is suitable for registration of presynaptic Ca2+ dynamics under both single nerve stimulus and rhythmic activity.

Best practice: surgeon driven application in pelvic operations

Abstract In applied biomedical engineering and medical industry the transfer of established technology towards customers’ needs is essential for successful development and therefore business opportunities. In chronological order, we can show the transfer of scientific results of neurophysiological research into an existing neuromonitoring system and product which can be used by non-experts in medical technology in the operating room environment. All neurophysiology functions were realized in an intuitive graphical user interface. To stimulate the autonomous nerves, a specialized parameter paradigm was used, different from motor nerve stimulation. In the background, a complex signal processing algorithm recorded smooth muscle and bladder manometry data in synchronized time and automatically detected neurophysiological signals. The acquired data was then presented in real-time. With this effort a complex scientific task could be simplified to a Yes/No statement to the end-user. Beside all the reduction of complexity, the scientific challenge was still obtained, as raw-data is still possible to be recorded.

Abstract 088: Chronic Efferent Vagal Stimulation Enhances Norepinephrine-mediated Inhibition of Splenic Pro-inflammatory Cytokine Release in Lupus Hypertension

Hypertension is prevalent in the autoimmune disease systemic lupus erythematosus (SLE), occurring with alarming frequency in reproductive-age women. Recent studies implicate the adaptive immune system in the development and maintenance of hypertension, and neuroimmune pathways may regulate this source of inflammation. One example is the cholinergic anti-inflammatory pathway (CAP), an endogenous nerve-to-spleen mechanism that regulates splenic pro-inflammatory cytokine release. We hypothesized that this pathway is impaired in SLE and that chronic stimulation of the CAP at the level of the efferent vagus nerve would attenuate hypertension in SLE. Starting at 30 and 32 weeks of age, female NZBWF1 SLE mice and NZW control mice were treated with the pharmacologic efferent vagal stimulators CNI-1493 (CNI; 8mg/kg; twice weekly; i.p.) or galantamine (GAL; 4mg/kg; daily; i.p.), or saline. At 34 weeks of age, we measured mean arterial pressure (MAP), finding that MAP (mmHg) in SLE mice was elevated compared to controls (139.83 ± 4.56 vs. 120.70 ± 2.96; n=4-6/group, p = 0.002), while the rise in MAP was prevented by CNI (134.45 ± 3.07)and GAL (129.25 ± 3.97) in SLE mice. We further hypothesized that splenocytes isolated from SLE mice conditioned by efferent vagal stimulation would release fewer pro-inflammatory cytokines in the presence of norepinephrine, which stimulates splenic β2 adrenergic receptors. We incubated isolated splenocytes for 24 hours at 37°C with and without norepinephrine (100 μM), then measured pro-inflammatory cytokines in the supernatant via ELISA. Compared to control mice, splenocytes from SLE mice secreted 70.7% and 146.5% higher concentrations of IL-6 and TNF-α (8.24 vs. 4.83 and 2.79 vs. 1.13 pg/mL, respectively; n=2/group) in the presence of norepinephrine. Compared to saline-treated SLE mice, splenocytes from CNI and GAL-treated SLE mice released fewer cytokines when incubated with norepinephrine (8.24 vs. 5.31 and 5.79 pg/mL IL-6; 2.79 vs. 2.18 and 0.81 pg/mL TNF-α; n=2/group). These in vivo and in vitro data suggest that stimulation of the CAP at the level of the efferent vagus may promote anti-inflammatory splenocyte activity, which may be protective against hypertension in the setting of chronic inflammation.

Cytoskeletal Protein Septins Participate in the Modulation of the Kinetics of Acetylcholine Quanta Release at Neuromuscular Junction

In the presynaptic nerve terminal, some families of cytoskeletal proteins can participate in the neurosecretion modulation. Septins, GTP-binding cytoskeletal proteins, form hetero-oligomeric complexes both among themselves and with other synaptic proteins. Previously, it was reported that in the cell cultures, septins can interact with SNARE complex, NSF and SNAP-25, suggesting septin involvement in the exocytosis of neuromediator. Here, we describe effects of septin blockade on the time course of acetylcholine quantal release at mice neuromuscular junction under different frequency stimulation of motor nerve. Forchlorfenuron (FCF), a synthetic cytokinin, is the inhibitor of septin polymerization which specifically impairs assembly and disassembly of septin hetero-oligomers without affecting the actin or tubulin polymerization. FCF in the concentrations from 20 to 100 μM decreased the intensity of the spontaneous and evoked release of acetylcholine quanta. Block of septin dynamics resulted in changes in the kinetics of quantal release: the synchronization of quanta secretion was observed at low and high frequencies of nerve stimulation.

Neuromodulation of pain

Neuromodulation is a burgeoning and exciting field that offers potential for innovative applications in medicine. The International Neuromodulation Society defines neuromodulation as electrical or chemical alteration of signal transmission within the nervous system by using implanted devices to affect improvement in symptoms and render optimal functioning to improve quality of life (Sakas et al. , 2007). Currently, spinal cord stimulation (SCS) leads the way as the most common application of neuromodulation, predominantly in cases of complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS). Motor cortex stimulation (MCS) and peripheral nerve stimulation (PNS) have also been used for treatment of intractable pain syndromes. Historically, even deep brain stimulation (DBS) has been employed for pain despite its most established application in current treatment of movement disorders such as Parkinson’s disease (PD). Neuromodulation of pain in palliative care, though not advocated previously because of cost and questionable efficacy with disease progression, may provide significant relief to many patients, especially as survival expectancy increases. This population typically has diminished organ reserve and particular vulnerability to drug-drug interactions from the exorbitant number of medications prescribed to manage conditions as well as the associated side effects from these medications. Thus, using a different modality of treatment such as an electrical stimulation device may be quite beneficial. Here, we explore the pre-clinical and clinical data that support the potential use of neuromodulation in palliation. We discuss the major modalities of stimulation (DBS, MCS, SCS, and PNS), examine their current uses, and assess the noted effects on refractory debilitating symptoms which may benefit people at the end of life. In addition, we outline the current limitations to widespread application of neuromodulation in palliative medicine.

Functional evidence for a direct excitatory projection from the lateral habenula to the ventral tegmental area in the rat.

The lateral habenula, a phylogenetically conserved epithalamic structure, is activated by aversive stimuli and reward omission. Excitatory efferents from the lateral habenula predominately inhibit midbrain dopamine neuronal firing through a disynaptic, feedforward inhibitory mechanism involving the rostromedial tegmental nucleus. However, the lateral habenula also directly targets dopamine neurons within the ventral tegmental area, suggesting that opposing actions may result from increased lateral habenula activity. In the present study, we tested the effect of habenular efferent stimulation on dopamine and nondopamine neurons in the ventral tegmental area of Sprague-Dawley rats using a parasagittal brain slice preparation. Single pulse stimulation of the fasciculus retroflexus excited 48% of dopamine neurons and 51% of nondopamine neurons in the ventral tegmental area of rat pups. These proportions were not altered by excision of the rostromedial tegmental nucleus and were evident in both cortical- and striatal-projecting dopamine neurons. Glutamate receptor antagonists blocked this excitation, and fasciculus retroflexus stimulation elicited evoked excitatory postsynaptic potentials with a nearly constant onset latency, indicative of a monosynaptic, glutamatergic connection. Comparison of responses in rat pups and young adults showed no significant difference in the proportion of neurons excited by fasciculus retroflexus stimulation. Our data indicate that the well-known, indirect inhibitory effect of lateral habenula activation on midbrain dopamine neurons is complemented by a significant, direct excitatory effect. This pathway may contribute to the role of midbrain dopamine neurons in processing aversive stimuli and salience.

Biophysical Processes in a Urinary Bladder Detrusor Smooth Muscle Cell during Rehabilitation Stimulation of Parasympathetic Efferents: a Simulation Study

In a computer model of an urinary bladder detrusor (UBD) smooth muscle cell (SMC), we investigated coupled changes in the membrane potential (MP), partial transmembrane currents, and intracellular calcium concentration ([Ca2 +]i), caused by parasympathetic stimulation. The respective data should help to determine the biophysical basis for the choice of parameters of medical rehabilitation electrical stimulation of the UBD. Ionotropic and metabotropic effects of such stimulation having different latency periods (LPs) were simulated by, respectively, an increase in the conductivity of purinoreceptor channels of the sarcolemma and a delayed (by 70 msec) increase in the permeability of calcium channels of the sarcoplasmic reticulum (store) sensitive to inositol triphosphate (IP3), the end-product of a chain of reactions triggered by activation of muscarinic cholinergic receptors. The modeled SMC responded to single stimulation by generation of action potential (AP) close in its parameters to those in the prototype. Application of long series of identical stimuli caused, after a transient interval, forced stationary oscillations of the MP and [Ca2 +]i. The magnitudes of the latter decreased, and the mean level increased with shortening of the interstimulus intervals (ISIs). It was found that the stimulation outcome needing prior experimental refining was determined by such parameters of the parasympathetic action as the durations of the purine and muscarinic components and the delay between these components. It has been shown that, during stimulation with ISIs shorter than the above-mentioned delay, the subsiquent stimulus activates P2X channels before expiration of the delay of the IP3-channel activation evoked by the preceding stimulus. This is actually equivalent to shortening of the interval between successive activations of P2X- and IP3-channels. Simple quantitative expressions were obtained for the parameters of stimulation; a given difference in the LPs of purine and muscarinic effects of parasympathetic stimulation allowed us to calculate the ISIs providing more efficient rehabilitation stimulation of the UBD parasympathetic nerves.

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation.

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.