Depression Of Amplitude Research Articles

Functional Impact of nTS Glutamate Stress on Respiration in an Alzheimer’s Disease Model

Alzheimer’s disease (AD) is closely associated with obstructive sleep apnea (OSA). Such hypoxic insults trigger glutamate release of chemoafferents into the nucleus tractus solitarii (nTS), an important upstream center of the chemoreflex. Potential alterations of glutamate handling in the nTS may lead to the respiratory dysfunction seen in AD patients. Using the streptozotocin (STZ)-induced rat model — an effective proxy for human AD — we studied the functional consequences of nTS glutamate stress on respiration. STZ-AD was induced in 6-week-old male Sprague Dawley rats via intracerebroventricular injections of 2 - 2.25 mg/kg STZ. After two weeks, EMG recordings of diaphragm activity served as surrogate for respiratory responses to glutamate microinjections (20 nL of 40 mM) into the caudal nTS. In a subset of rats, chemoafferent terminals were labeled with the fluorescent tracer DiI to permit patch clamp recordings of identified 2nd order nTS neurons participating in the chemoreflex loop. Evoked glutamatergic excitatory postsynaptic currents (TS-EPSCs) were generated via tractus solitarii stimulation at frequencies (10 - 40 Hz) typical for afferent discharge during hypoxia. Acute glutamate injections into the caudal nTS increased respiratory frequency by 15 - 20 breaths per minute. The response magnitude was similar between CTL and STZ-AD animals. Excitatory stress with repeated glutamate injections (5 min. apart) evoked a reliable respiratory response in CTL that slowly declined to ~65% from its maximum over the course of 10 injections. In contrast, the decline of respiratory response in STZ-AD was more pronounced and occurred significantly earlier than in CTL, indicating altered glutamate handling in the caudal nTS of STZ-AD rats. Next, we used patch clamp electrophysiology to analyze increased glutamate release of chemoafferents onto 2nd order nTS neurons. High frequency stimulation of chemoafferents induced a successive depression of TS-EPSC amplitude in nTS neurons. TS-EPSC depression was significantly stronger in STZ-AD and may be due to altered glutamate handling at the synapse. Western Blot analysis of STZ-AD brainstem tissue including the nTS revealed a significant increase in glial fibrillary acidic protein (GFAP) expression and a decrease of excitatory amino acid transporters (EAATs) expression, suggesting astrocyte involvement in compromised nTS glutamate handling in STZ-AD. In summary, the STZ-AD model showed reduced respiratory responses to glutamate stress in the caudal nTS. The altered stress response may come from enhanced depression of TS-EPSC amplitude at nTS neurons in the chemoreflex. Altered astrocytic glutamate removal from the synaptic cleft may contribute to TS-EPSC depression. Together, altered glutamate handling in a respiratory brainstem center may contribute to OSA in AD patients. NIH R15AG065927 (TDO & DO), KCOM Biomedical Graduate Program (RKT &TDO), ATSU Research Support (SKRC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hyperthyroidism-Induced Upregulation of Neurodegeneration-Related Gene Expression in Metaplasticity-Induced Hippocampus

Introduction: Thyroid hormones, which produce critical changes in our bodies even when their physiological levels alter slightly, are crucial hormones that influence gene transcription. Neuronal plasticity, on the other hand, requires both the activation of local proteins as well as protein translation and transcription in response to external signals. So far, no study has examined metaplastic long-term potentiation (LTP) and related gene expression levels in a hyperthyroid experimental model. Methods: The Wistar male rats were administered 0.2 mg/kg/day of <sc>l</sc>-thyroxine for 21 days to induce hyperthyroidism. Perforant path was primed with 1-Hz low-frequency stimuli (LFS) for 900 s to investigate metaplasticity responses. The LFS was followed by high-frequency stimuli (HFS, 100 Hz) after 5 min. Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were recorded from the granule cell layer of the dentate gyrus. The mRNA levels of genes related to neurodegeneration (Gsk-3β, Cdk5, Akt1, Mapt, p35, Capn1, Bace1, and Psen2) were measured using the RT-PCR method for the stimulated hippocampus. Results: Similar to euthyroid rats, hyperthyroid animals had a lower EPSP slope and PS after LFS. Depression of EPSP prevented subsequently induced EPSP-LTP, although HFS was able to elicit PS-LTP despite depression of PS amplitude in both groups. Despite similarities in metaplastic LTP responses, these electrophysiological findings were accompanied by increased Akt, Bace1, Cdk5, and p35-mRNA expressions and decreased Gsk-3β mRNA expression in hyperthyroid rats’ hippocampus. Conclusion: These data support the view that in thyroid hormone excess, the mechanism that keeps synaptic efficacy within a dynamic range occurs concurrently with increased mRNA expression of neurodegeneration-related genes. Our study encourages further examination of the increased risk of neurodegenerative disease in hyperthyroidism.

Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects.

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.

Total electron content depression in the nightside Martian ionosphere: statistical results from Mars Express MARSIS measurements and implications

ABSTRACT Thermal electron depression and energetic electron depletion are two well-known features of the nightside Martian ionosphere. While the latter has been extensively studied in the past, there is no report of systematic and firm identification of the former and hence the correlation between them is unknown. Applying an automatic procedure to the Mars Express total electron content (TEC) measurements, we identify a large number of TEC depression features that amount to one-third of the available nightside measurements. Similar to the observation of energetic electron depletion, large amplitude TEC depression is more frequently observed near strong magnetic fields, as an expected result of the established solar-wind-driven scenario that the shielding of precipitating electrons by closed magnetic loops is responsible for the observed reduction in thermal electron density. However, small amplitude depression appears to be uniformly distributed across the Martian surface, implying an alternative origin yet to be determined. Contrary to our expectation, TEC depression and energetic electron depletion are not usually collocated, but this dilemma may simply reflect the complexity of the magnetic field topology with respect to the spacecraft trajectory.

Basal and Hypoxic Respiratory Behaviors in Aged 6‐OHDA‐Induced SN Lesion PD Rat Model: Effects of the 5‐HT1A Receptor Agonist Buspirone

Parkinson’s disease (PD) is progressive neurodegenerative disease, with the diagnosis of idiopathic PD occurring in humans at ~60 years of age. Most studies, however, use young adult (≤3 month old) rats to investigate PD‐related abnormalities in various physiological systems, with the most commonly used experimental rat PD model being generated by unilateral injection of the neurotoxin 6‐hydroxydopamine (6‐OHDA) into specific regions of the nigrostriatal pathway. While this model results in the loss of dopaminergic neurons and the subsequent changes in downstream neurotransmitter signaling that are characteristic of PD, it does not consider potential contributions of physical changes to the brain and neurotransmitter signaling that are part of normal aging on the progression of PD. To better understand age‐related influences and potential contributions of PD‐related abnormalities in serotonergic (5‐HT) neurotransmission on respiratory dysfunction (which is a common non‐motor symptom) in PD, we investigated basal and hypoxic (12% O2; 90s) respiratory behaviors before and after acute administration of the frequently prescribed anxiolytic 5‐HT1A receptor agonist buspirone (BUS; 0.5 mg/kg, iv) in an aged (~9 month old) female Sprague‐Dawley PD rat model produced by unilateral 6‐OHDA injection into the substantia nigra (SN). For these experiments, diaphragm EMG activity was recorded and quantified from spontaneously breathing urethane‐anesthetized rats at 2‐weeks after SN 6‐OHDA or vehicle (control) injections. We found that 6‐OHDA‐injected rats have a lower basal breathing frequency (P&lt;0.05) due to shorter expiratory duration (TE; P&lt;0.05) than vehicle‐injected rats, but both 6‐OHDA‐ and vehicle‐injected rats exhibit significant increases in breathing frequency (P≤0.001) and EMG amplitude (P≤0.023) during hypoxia; the magnitude of the peak frequency increase in 6‐OHDA‐injected rats was slightly greater (P=0.083). Both 6‐OHDA‐ and vehicle‐injected rats also showed similar post‐hypoxic frequency decline (P≤0.003), but only vehicle‐injected rats displayed a slight and sustained post‐hypoxic amplitude depression (P&lt;0.1). In vehicle‐injected rats, acute BUS injection produced a progressive decrease in basal EMG amplitude (P=0.066) and a persistent increase in breathing frequency (P=0.064) by decreasing inspiratory duration (TI; P&lt;0.001) while in 6‐OHDA‐injected rats, a transient initial increase in EMG amplitude (P=0.043) and a persistent decrease in TI (P=0.005) and TE (P=0.089) were noted. In both 6‐OHDA‐ and vehicle‐injected rats, BUS injection also slightly exaggerated the initial hypoxic frequency increase, but blunted the amplitude increase with amplitude progressively declining to near pre‐hypoxic levels before the end of the hypoxic exposure. BUS injection also shortened the duration of post‐hypoxic EMG amplitude depression in vehicle‐injected rats. These data demonstrate that some differences in basal and hypoxic respiratory behaviors exist between older 6‐OHDA‐ and vehicle‐injected rats, and that some respiratory behaviors of these rat models are differentially impacted by BUS‐induced effects on respiratory control. We suggest that this older PD rat model be further evaluated.

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity.

Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8–37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.

An optoelectronic notch (‘dip’) phenomenon in the heterodyne photocarrier radiometry frequency response of Si wafers: a route to quantitative trap-state dynamic processes in semiconductors

An anomaly was observed in the heterodyne photocarrier radiometry (HePCR) frequency response of Si wafers in the form of a signal amplitude depression (‘dip’) accompanied by a 180° phase transition. This phenomenon resembles an electronic notch filter and was investigated experimentally and theoretically by invoking free-carrier-density-wave (CDW) kinetics in generic semiconductor systems. Both homodyne PCR and HePCR signals were obtained from n- and p-type wafers of different resistivities. Dynamic nonlinear rate-equation models with two bandgap carrier traps were introduced and analytical zeroth and first-order CDW solutions were obtained in the frequency domain. The experimental frequency responses of the HePCR optoelectronic notch phenomenon were found to be in very good agreement with the theory. Characteristic CDW recombination and trap capture and emission characteristic times were obtained and studied as functions of the illuminating laser intensity. The present newly observed HePCR notch phenomenon has revealed a new mechanism of nonlinear contributions due to trap-state-related CDW dynamics in semiconductors superposed on the well-known nonlinear electron-hole recombination interactions that give rise to non-zero HePCR signals. The implications of this notch phenomenon are discussed in terms of its importance in providing physical insights into photocarrier dynamic interactions with traps, leading to identification of active CDW trap-state numbers and precision measurements of their kinetic parameters, carrier capture and emission coefficients, and quantitative trap densities that determine the optoelectronic quality of semiconductors.

An experimental study on intraoperative recovery of recurrent laryngeal nerve function.

ObjectiveIf bilateral thyroid surgery is planned and staged thyroidectomy considered in case of loss of neuromonitoring signal (LOS), a waiting time of 20 minutes is suggested for evaluation of early nerve recovery. This recommendation is based on clinical observations and has not been thoroughly validated experimentally.MethodsSixteen pigs were randomly studied, and electromyogram (EMG) was continuously recorded during traction injury until an amplitude decrease of 70% from baseline (BL) (16 nerves) or LOS (16 nerves), and further during 40‐minute recovery time. At the end of the experiments, vocal cord twitch was evaluated by video‐laryngoscopy.ResultsIn the 70% group, 8 of 16 nerves recovered to or above an amplitude of 50% of baseline after 20 minutes and finally one more after 40 minutes. In the LOS group, only one nerve showed recovery after 20 minutes and one more after 40 minutes. Video‐laryngoscopy revealed good or strong vocal cord twitches, in 10 of 14 nerves in the 70% group and in only 2 of 14 nerves in the LOS group.ConclusionsThe overall intraoperative recovery was low after LOS. Even after 70% amplitude depression, only half of the nerves showed recovery to amplitudes ≥50% of BL. Nerve recovery is dynamic, and a waiting time of 20 minutes seems appropriate for the identification of early nerve recovery before decisions are taken to continue or terminate surgery. The final EMG amplitude was not always well correlated with estimated vocal cord twitch, evaluated by video‐laryngoscopy. This observation needs further investigation.

A stimulus rate that is not influenced by homosynaptic post-activation depression in chronic stroke

Purpose To determine a stimulus rate that is not influenced by homosynaptic post-activation depression for H-reflex studies in patients with chronic spasticity. Materials and methods A cohort of 15 chronic stroke patients with soleus spasticity who received inpatient treatment at our rehabilitation centre participated in this study. The effect of stimulus frequency related depression on H-reflex size was tested using four different stimulus rates (0.1, 0.2, 0.3 and 1 Hz). The affected sides stibial nerve was stimulated by a bipolar electrode. The H-reflex was recorded from the affected sideed sidee sidehe affected smine stimulus frequency related depression of H-reflex size, amplitude of the first H-reflex response (H1) was used as control and amplitude of the second H-reflex response (H2) as test. Results H2 amplitude for frequency of 1 Hz, 0.3 Hz, 0.2 Hz and 0.1 Hz were 74.3, 84.1, 85.5 and 92.7% of H1, respectively. Depression of H2 amplitude was statistically significant for 1 Hz, 0.3 Hz and 0.2 Hz (p < 0.001, p = 0.002, p = 0.024, respectively). Conclusions Higher frequency stimulation of Ia afferents than 0.1 Hz induced a stimulus frequency-related depression of H-reflex size in patients with chronic spasticity. The optimal stimulus rate for H-reflex was found to be 0.1 Hz.

Deconstructing circadian disruption: Assessing the contribution of reduced peripheral oscillator amplitude on obesity and glucose intolerance in mice.

Disturbing the circadian regulation of physiology by disruption of the rhythmic environment is associated with adverse health outcomes but the underlying mechanisms are unknown. Here, the response of central and peripheral circadian clocks to an advance or delay of the light-dark cycle was determined in mice. This identified transient damping of peripheral clocks as a consequence of an advanced light-dark cycle. Similar depression of peripheral rhythm amplitude was observed in mice exposed to repeated phase shifts. To assess the metabolic consequences of such peripheral amplitude depression in isolation, temporally chimeric mice lacking a functional central clock (Vgat-Cre+ Bmal1fl/fl ) were housed in the absence of environmental rhythmicity. In vivo PER2::LUC bioluminescence imaging of anesthetized and freely moving mice revealed that this resulted in a state of peripheral amplitude depression, similar in severity to that observed transiently following an advance of the light-dark cycle. Surprisingly, our mice did not show alterations in body mass or glucose tolerance in males or females on regular or high-fat diets. Overall, our results identify transient damping of peripheral rhythm amplitude as a consequence of exposure to an advanced light-dark cycle but chronic damping of peripheral clocks in isolation is insufficient to induce adverse metabolic outcomes in mice.

Latitudinal variation of Pc3–Pc5 geomagnetic pulsation amplitude across the dip equator in central South America

Abstract. In order to clarify the equatorial electrojet effects on ground magnetic pulsations in central South America, we statistically analyzed the amplitude structure of Pc3 and Pc5 pulsations recorded during days considered quiet to moderately disturbed at multiple equatorial stations nearly aligned along the 10∘ magnetic meridian. It was observed that Pc3 amplitudes are attenuated around noon at the dip equator for periods shorter than ∼35 s. It is proposed that daytime Pc3s are related to MHD (magnetohydrodynamic) compressional wave vertically incident on the ionosphere, with the screening effect induced by enhanced conductivity in the dip equator causing wave attenuation. Daytime Pc5s showed amplitude enhancement at all equatorial stations, which can be explained by the model of waves excited at higher latitudes and propagating equatorward in an Earth–ionosphere waveguide. However, a slight depression in Pc5 amplitude compared to neighboring equatorial stations and a phase lag in relation to an off-equatorial station were detected at the dip equator. This wave amplitude depression in the Pc5 frequency band cannot be explained by the ionospheric waveguide model alone, and we propose that an alternative propagation model that allows ULF (ultra-low-frequency) waves to penetrate directly from the magnetosphere to low latitudes could be operating simultaneously to produce these features at the dip equator. Significant effects of the sunrise terminator on Pc3 pulsations were also observed at the stations closest to the dip equator. Contrary to what is reported at other longitudes, in central South America the sunrise effect decreases the D∕H amplitude ratio. We suggest that these differences may arise from the unique characteristics of this sector, with a strong longitudinal variation in the magnetic declination and precipitation of energetic particles due to the presence of the South Atlantic Magnetic Anomaly (SAMA). The H-component amplification can be explained by enhancements of the zonal electric field near the magnetic equator driven by F-region neutral winds and waves in the fast-mode of propagation during sunrise.

Adaptations to Oral and Pharyngeal Swallowing Function Induced by Injury to the Mylohyoid Muscle.

Muscle injury is a frequent side effect of radiation treatment for head and neck cancer. To understand the pathophysiology of injury-related dysfunction, we investigated the effects of a single muscle injury to the mylohyoid on oropharyngeal swallowing function in the rat. The mylohyoid protects the airway from food/liquid via hyolaryngeal elevation and plays an active role during both oral and pharyngeal swallowing. We hypothesized (1) that fibrosis to the mylohyoid alters swallowing bolus flow and licking patterns and (2) that injury to the mylohyoid changes normal activity of submental, laryngeal, and pharyngeal muscles during swallowing. A chilled cryoprobe was applied to the rat mylohyoid muscle to create a localized injury. One and two weeks after injury, swallowing bolus transit was assessed via videofluoroscopy and licking behavior via an electrical lick sensor. The motor activity of five swallow-related muscles was analyzed immediately after injury using electromyography (EMG). Comparisons were made pre- and post-injury. Fibrosis was confirmed in the mylohyoid at 2 weeks after injury by measuring collagen content. One week after injury, bolus size decreased, swallowing rate reduced, and licking patterns were altered. Immediately post-injury, there was a significant depression in mylohyoid and thyropharyngeus EMG amplitudes during swallowing. Our results demonstrated that injury to the mylohyoid is sufficient to cause changes in deglutition. These disruptions in oral and pharyngeal swallowing were detected prior to long-term fibrotic changes, including delays in tongue movement, alterations in bolus flow, and changes in sensorimotor function. Therefore, injuring a single important swallowing muscle can have dramatic clinical effects.

Impaired Choroidal Blood Flow in Adolescents with Essential Arterial Hypertension

Arterial hypertension is a problem not only for adults, but also for children, but there are very few data on changes in the organ of vision under the influence of an elevated level of blood pressure in children.The aim of the work is to identify disturbances of the choroidal blood flow in children and adolescents with essential arterial hypertension.Methods. Fifty patients with essential arterial hypertension were examined. The age of patients ranged from 10 to 17 years, the duration of the disease ranged from 2 months to 8 years. All patients underwent color Doppler mapping of the orbital vessels, registration of the oscillatory potentials of the ERG.Results. It was revealed that increased arterial pressure causes retinal and choroidal ischemia, which is accompanied primarily by impaired blood flow in the orbital vessels and is reflected in a decrease in the amplitude and deformation of the peaks of the ERG oscillatory potentials.Conclusion. Hypertension causes and supports retinal and choroidal ischemia, which is accompanied primarily by impaired blood flow in the orbital vessels, functional depression of photoreceptors, ganglion cells and neuroglia of the retina, aggravating the identified changes as the experience of essential hypertension increases. A marker of chorioretinal ischemia is amplitude depression, a change in the shape of the teeth of the oscillatory potentials of the ERG, which indicates a decrease in the functional activity of the retinal ganglion complex.That is, these changes can be considered as a predictor of hypertensive angioretinopathy in children and adolescents with essential arterial hypertension.

Glutamate/GABA co-release selectively influences postsynaptic glutamate receptors in mouse cortical neurons

Cultured rat cortical neurons co-expressing VGLUT1 and VGAT (mixed synapses) co-release Glu and GABA. Here, mixed synapses were studied in cultured mouse cortical neurons to verify whether in mice mixed synapses co-release Glu and GABA, and to gain insight into how they may influence excitation/inhibition balance. Results showed the existence of synapses and autapses that co-release Glu and GABA in cultured mouse cortical neurons, and the ability of both neurotransmitters to evoke postsynaptic responses mediated by ionotropic receptors. We studied the short-term plasticity of glutamatergic, GABAergic, and mixed responses and we found that the kinetics of mixPSC amplitude depression was similar to that observed in EPSCs, but it was different from that of IPSCs. We found similar presynaptic release characteristics in glutamatergic and mixed synapses. Analysis of postsynaptic features, obtained by measuring AMPAR- and NMDAR-mediated currents, showed that AMPAR-mediated currents were significantly higher in pure glutamatergic than in mixed synapses, whereas NMDAR-mediated currents were not significantly different from those measured in mixed synapses. Overall, our findings demonstrate that glutamatergic and mixed synapses share similar electrophysiological properties. However, co-release of GABA and Glu influences postsynaptic ionotropic glutamatergic receptor subtypes, thus selectively influencing AMPAR-mediated currents. These findings strengthen the view that mixed neurons can play a key role in CNS development and in maintaining the excitation-inhibition balance.

Vocal cord function during recurrent laryngeal nerve injury assessed by accelerometry and EMG.

Gradual impairment of nerve conduction is expected to be tightly associated with simultaneous gradual loss of vocal cord contractility, related to the fact that injured axons are connected to a defined number of muscle cells. In clinical studies, there is a time gap between observed adverse electromyographic (EMG) changes and examination of vocal cord function. This study evaluates the impact of intraoperative EMG changes on synchronous vocal cord contractility by simultaneous use of continuous intraoperative neuromonitoring (C-IONM) and accelerometry for registration of actual vocal cord function at a given change of EMG amplitude. EMG was obtained following vagus nerve stimulation by use of C-IONM. A vocal cord accelerometer probe that could be attached to the vocal cords was developed based on a LIS3DH ultra low-power high performance three axis linear accelerometer (STMicroelectronics, Geneva, Switzerland). Accelerometer data were registered continuously together with EMG data during traction injury of the recurrent laryngeal nerve (RLN) until an amplitude depression ≤100 μV. Six RLN from four immature domestic pigs were studied. Vocal cord contractility assessed by vocal cord accelerometry decreased in parallel with EMG amplitude, with significant correlations ranging from 0.707 to 0.968. Decrease of EMG amplitude during traction injury to the RLN injury is closely associated with a parallel drop in vocal cord contractility. NA Laryngoscope, 130:1090-1096, 2020.

Oxysterol modulates neurotransmission via liver-X receptor/NO synthase-dependent pathway at the mouse neuromuscular junctions

Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of prolonged application of 24S-HCh (2.5 h, 0.4 μM) on the neurotransmission in the mice diaphragm. 24S-HCh enhanced the depression of EPP amplitude (indicator of neurotransmitter release) and suppressed the FM1-43 dye unloading from nerve terminals (indicator of exocytosis) during electrical nerve stimulation at 20 Hz, without affecting miniature EPP amplitude and frequency. Comparison of the rates of neurotransmitter and FM1-43 releases suggested an increase in time required for the synaptic vesicle reuse. Additionally, 24S-HCh potentiated an increase in DAF-FM fluorescence (a NO-sensitive marker) in response to 20 Hz stimulation. All effects of 24S-HCh were completely prevented by liver X receptor antagonist. Either inhibitors of NO synthases (TRIM, cavtratin) or protein synthesis blocker counteracted the 24S-HCh-mediated enhancement in DAF-FM fluorescence, while inhibition of NO production with l-NAME or cavtratin and extracellular NO chelation suppressed the effect of 24S-HCh on FM1-43 dye loss during 20 Hz activity. Pretreatment for 5 days with inhibitor of 24S-HCh synthesis (voriconazole) had opposite effects on the FM1-43 unloading and NO synthesis. These data suggest that prolonged exposure to 24S-HCh attenuates recruitment of synaptic vesicle to exocytosis during 20 Hz stimulation acting via liver Х receptor/NO-dependent signaling.

Detecting Cortical Spreading Depolarization with Full Band Scalp Electroencephalography: An Illusion?

There is strong evidence suggesting detrimental effects of cortical spreading depolarization (CSD) in patients with acute ischemic stroke and severe traumatic brain injury. Previous studies implicated scalp electroencephalography (EEG) features to be correlates of CSD based on retrospective analysis of EEG epochs after having detected "CSD" in time aligned electrocorticography. We studied the feasibility of CSD detection in a prospective cohort study with continuous EEG in 18 patients with acute ischemic stroke and 18 with acute severe traumatic brain injury. Full band EEG with 21 silver/silver chloride electrodes was started within 48 h since symptom onset. Five additional electrodes were used above the infarct. We visually analyzed all raw EEG data in epochs of 1 h. Inspection was directed at detection of the typical combination of CSD characteristics, i.e., (i) a large slow potential change (SPC) accompanied by a simultaneous amplitude depression of >1Hz activity, (ii) focal presentation, and (iii) spread reflected as appearance on neighboring electrodes with a delay. In 3,035 one-hour EEG epochs, infraslow activity (ISA) was present in half to three quarters of the registration time. Typically, activity was intermittent with amplitudes of 40-220 µV, approximately half was oscillatory. There was no specific spatial distribution. Relevant changes of ISA were always visible in multiple electrodes, and not focal, as expected in CSD. ISA appearing as "SPC" was mostly associated with an amplitude increase of faster activities, and never with suppression. In all patients, depressions of spontaneous brain activity occurred. However, these were not accompanied by simultaneous SPC, occurred simultaneously on all channels, and were not focal, let alone spread, as expected in CSD. With full band scalp EEG in patients with cortical ischemic stroke or traumatic brain injury, we observed various ISA, probably modulating cortical excitability. However, we were unable to identify unambiguous characteristics of CSD.

Histopathological and functional changes in a single-dose model of combretastatin A4 disodium phosphate-induced myocardial damage in rats.

Cardiotoxicity is a concern in the development of microtubule-disassembling agents (MDAs) as vascular-disrupting agents of tumors. This study investigated cardiotoxicity in rats induced by a single-dose of combretastatin A4 disodium phosphate (CA4DP), an MDA and discussed the use of this rat model in nonclinical studies of MDAs. First, CA4DP (120 mg/kg) was administered to rats intravenously, and cardiac histopathology and blood biomarkers were examined after 0.5, 24, and 72 h. Next, CA4DP (120 mg/kg) was administered to rats intravenously, and the electrocardiography and echocardiography results were analyzed. The results showed that at 0.5 h after dosing, plasma creatine kinase (CK), CK-muscle/brain (CK-MB), and fatty acid binding protein 3 levels increased. At 24 h, lactate dehydrogenase (LDH)-1, CK, and CK-MB levels increased, and multifocal vacuolar degeneration of myocardial cells was observed in the apical inner layer. At 72 h, LDH-1 levels were increased, and multifocal myocardial necrosis was observed in the interventricular septum and inner layer of the apex of left ventricular wall. Furthermore, at 0.5 h, heart rate (HR), ejection fraction (EF), and cardiac output (CO) decreased. At 24 h, CO decreased. Finally, at 72 h, HR, EF, and CO decreased, and depression of the T-wave amplitude was observed. In conclusion, myocardial injury, bradycardia, and depressed cardiac function were induced in rats by a single-dose of CA4DP. The lesion distribution and electrocardiographic features suggested that myocardial injury was induced by ischemia. These findings are similar to MDA-induced cardiotoxicity in humans, and this rat model will prove useful in studies of the cardiotoxicity in humans.

Seric Concentration of Troponin I and Electrocardiographic Tracing in Dogs Submitted to Long-Term Sedation during 24 Hours

Background: General anesthetics and sedatives are commonly used for long-term sedation in veterinary medicine; however, they can lead to cardiac suppression. Cardiac troponin I is a biomarker used to detect myocardial pathology, monitor treatment, and assess outcomes in veterinary patients. The aim of this study was to evaluate the serum concentration of troponin I (cTnI), the electrocardiographic (ECG) tracing, and the ventricular stroke work index in dogs undergoing two long-term sedation protocols over 24 h.Materials, Methods &amp; Results: Twelve healthy mongrel dogs with an average weight of 13.2 ± 2.3 Kg were admitted for this study. Twenty-four h before the experiment began (M-24), venous blood samples were collected for chemiluminescent cTnI evaluation and ECG data were obtained, specifically heart rate (HR); P, PR, QRS and T wave duration; P, R, T wave amplitude; and ST segment depression. On the day of the experiment, the animals were anaesthetized with propofol and isoflurane, and instrumented. After instrumentation, right and left ventricular stroke work index (RVSWI and LVSWI respectively) and intrapulmonary shunt (Qs/Qt) were performed as baseline parameters. The isoflurane was then discontinued and the animals randomly allocated to two groups (n = 6 each): Midazolam and fentanyl group (GMF), in which the animals received a bolus and continuous rate infusion (CRI) of midazolam (0.5 mg/kg and 0.5 mg/kg/h) and fentanyl (5 µg/kg and 10 µg/kg/h) or ketamine and morphine group (GKM), in which the animals received a bolus and CRI of ketamine (1 mg/kg and 0.6 mg/kg/h) and morphine (0.5 mg/kg and 0.26 mg/kg/h). Both groups also received propofol as a bolus and CRI (3 mg/kg and 0.3 mg/ kg/min) over 24 h. The ECG and cTnI parameters were evaluated at 6, 12, and 24 h during CRI (M6, M12, and M24) and 12 and 24 h after the end of infusion (T12 and T24). The hemodynamic parameters RVSWI, LVSWI, and Qs/Qt were evaluated every 2 h until the end of CRI. There was a non-significant increase in cTnI from M6 in both groups; however, a significant increase was only observed in GMF between M-24 and T12. During sedation, HR decreased an average of 46% in GKM and 51% in GMF compared to M-24. The QT interval (milliseconds) increased in both groups after CRI started, returning to baseline values at T24. There were no differences in P, QRS, and T wave amplitude or ST segment depression in either group.Discussion: The serum concentration of cTnI increased in GMF at T12, more probably due to hemodynamic changes during sedation rather than myocardial lesions, since the increase was relatively mild. A greater hemodynamic change was observed in GMF, with a greater increase in RVSWI compared to baseline than GKM, which may reflect an increase in cardiac effort and possibly cTnI release; however, in both groups, the cTnI values remained within the acceptable values for the species. Bradycardia was reported during long-term sedation, which may be due to the synergism between opioids as a result of vagal stimulation, central sympathetic inhibition, and a possible action on cardiac receptors, and propofol due to the inhibitory effect on the sympathetic nervous system. Increases in QT interval did not lead to marked changes in this study. T wave amplitude and ST segment depression remained unchanged and within acceptable values for the species, and thus agreed with cTnI data, implying that no myocardial lesions were produced by these protocols. It has been established that for both protocols, cTnI remained within physiological ranges for healthy dogs, and therefore, these methods could be used safely for long-term sedation without producing hypoxia/ischemia of the myocardium or ST-segment depression.

The intensity of continuous theta burst stimulation, but not the waveform used to elicit motor evoked potentials, influences its outcome in the human motor cortex

BackgroundResponses to continuous theta burst stimulation (cTBS) applied to the human primary motor cortex are highly variable between individuals. However, little is known about how to improve the after-effects of cTBS by adjusting the protocol characteristics. ObjectiveWe examined whether current directions adopted in the measurement of cortical motor excitability indexed as motor evoked potentials (MEPs) affect the responses to cTBS. We also tested whether the stimulus intensity of cTBS influences the after-effects. MethodsThirty-one healthy volunteers participated. The after-effects of cTBS with the conventional intensity of 80% of individual active motor threshold (AMT) (cTBS80%) were tested by measuring MEP amplitudes induced by not only posterior-anterior (PA) but also anterior-posterior (AP) and biphasic (PA-AP) currents. We also investigated cTBS with 65% AMT (cTBS65%) and 100% AMT (cTBS100%) in subjects who showed depression of MEP amplitudes after cTBS80%, as well as cTBS65% in subjects in whom facilitation of MEPs was induced by cTBS80%. ResultsCurrent directions in MEP measurement had no influence on the cTBS responses. In subjects whose MEPs were depressed by cTBS80%, cTBS100% partly induced MEP facilitation, while cTBS65% abolished the after-effects. In subjects who showed MEP facilitation by cTBS80%, cTBS65% partly induced MEP depression. ConclusionsStimulus intensity of cTBS influenced the responses to cTBS, and lowering stimulus intensity induced the expected after-effects of cTBS in some subjects.