Response of Vestibular-Nerve Afferents to Active and Passive Rotations Under Normal Conditions and After Unilateral Labyrinthectomy

2007 ◽  
Vol 97 (2) ◽  
pp. 1503-1514 ◽  
Author(s):  
Soroush G. Sadeghi ◽  
Lloyd B. Minor ◽  
Kathleen E. Cullen

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1–12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5–15 Hz (20–80°/s) and fast whole-body rotations reaching velocities of 500°/s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of ≤2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

2009 ◽  
Vol 102 (5) ◽  
pp. 2693-2703 ◽  
Author(s):  
Soroush G. Sadeghi ◽  
Jay M. Goldberg ◽  
Lloyd B. Minor ◽  
Kathleen E. Cullen

Mechanical occlusion (plugging) of the slender ducts of semicircular canals has been used in the clinic as well as in basic vestibular research. Here, we investigated the effect of canal plugging in two macaque monkeys on the horizontal vestibuloocular reflex (VOR) and the responses of vestibular-nerve afferents during passive head rotations. Afferent responses to active head movements were also studied. The horizontal VOR gain decreased after plugging to <0.1 for frequencies <2 Hz but rose to about 0.6 as frequency was increased to 15 Hz. Afferents innervating plugged horizontal canals had response sensitivities that increased with the frequency of passive rotations from <0.01 (spikes/s)/(°/s) at 0.5 Hz to values of about 0.2 and 0.5 (spikes/s)/(°/s) at 8 Hz for regular and irregular afferents, respectively (<50% of responses in controls). An increase in phase lead was also noted following plugging in afferent discharge, but not in the VOR. Because the phase discrepancy between the VOR and afferent discharge is much larger than that seen in control animals, this suggests that central adaptation shapes VOR dynamics following plugging. The effect of canal plugging on afferent responses can be modeled as an increase in stiffness and a reduction in the dominant time constant and gain in the transfer function describing canal dynamics. Responses were also evident during active head rotations, consistent with the frequency content of these movements. We conclude that canal plugging in macaques is effective only at frequencies <2 Hz. At higher frequencies, afferents show significant responses, with a nearly 90° phase lead, such that they encode near-rotational acceleration. Our results demonstrate that afferents innervating plugged canals respond robustly during voluntary movements, a finding that has implications for understanding the effects of canal plugging in clinical practice.


2020 ◽  
Vol 54 (5) ◽  
pp. 15-22
Author(s):  
I.M. Larina ◽  
◽  
D.N. Kashirina ◽  
K.S. Kireev ◽  
A.I. Grigoriev ◽  
...  

We performed the first ever comparative analysis of modifications in the proteome, ionogram and some other blood plasma biochemical indices of 18 male cosmonauts (44 ± 6 years of age) before and after maiden or repeated long-term missions to the Russian segment of the International space station (ISS RS). Levels of proteins, substrates and ions as well as chemical components were measured using the LC-MS-based proteomics and routine biochemical techniques. A total of 256 to 281 indices were investigated with the methods of descriptive statistic, regression analysis, and access to bioinformatics resources. It was shown that blood indices recovery from the maiden and repeated missions reflects changes in the body systems and goes at a various speed. The results of measurements made prior to launch and on day 7 after landing are dependent on the number of missions. The bioinformatics techniques showed that after maiden missions both the mediator proteins of alkaline phosphatase (AP) and blood proteins with reliably changing concentrations are associated with the bio-processes including stress, metabolism and DNA reparation, apoptosis, catabolism and proteolysis. During early re-adaptation from repeated missions the AP level was affected by bone remodeling, phosphorylation, angiogenesis and coagulation cascade suggesting a distinct and urgent trigger of the processes of bone structure and mineralization.


2021 ◽  
Vol 8 ◽  
Author(s):  
Franziska Grundler ◽  
Gilles-Eric Séralini ◽  
Robin Mesnage ◽  
Vincent Peynet ◽  
Françoise Wilhelmi de Toledo

Background: Dietary exposure to environmental pollutants in humans is an important public health concern. While long-term fasting interrupts the dietary exposure to these substances, fat mobilization as an energy source may also release bioaccumulated substances. This was, to our knowledge, only investigated in obese people decades ago. This study explored the effects of 10-days fasting on the excretion of heavy metals and glyphosate.Methods: Urinary levels of arsenic, chromium, cobalt, lead, nickel, mercury and glyphosate were measured before and after 10 fasting days in 109 healthy subjects. Additionally, hair analysis was done before and ten weeks after fasting in 22 subjects.Results: Fasting caused a decrease in body weight, and in urinary arsenic (by 72%) and nickel (by 15%) concentrations. A decrease in lead hair concentrations (by 30%) was documented. Urinary mercury levels were unchanged for chromium, cobalt and glyphosate, which were undetectable in most of the subjects. Additionally, fatigue, sleep disorders, headache and hunger were reduced. Body discomfort symptoms diminished four weeks after food reintroduction.Conclusions: The results of this study provide the first insights into the changes in heavy metal excretion caused by long-term fasting. Further studies focusing on the kinetics of efflux between different compartments of the body are needed.Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS00016657, identifier: DRKS00016657.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 261-261 ◽  
Author(s):  
Douglas Campbell ◽  
Dhanusha Sabanathan ◽  
Howard Gurney ◽  
David Gillatt ◽  
Marko Trifunovic ◽  
...  

261 Background: Miltuximab is a chimeric antibody targeting Glypican-1 which is overexpressed in prostate cancer. Miltuximab has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. Methods: Metastatic patients (prostate, pancreatic and bladder) were dosed with unlabelled Miltuximabfollowed by the infusion of 1 mg/250MBq 67Ga-Miltuximab. Patients underwent whole body gamma and SPECT/CT scans up to 144 hours post-infusion. Standard of care imaging was performed at least 14 days before and after participation. Safety was evaluated by an external monitoring committee. Total organ exposure was determined by dosimetry of whole-body gamma scans. Antibody pharmacokinetics were also determined. Results: 12 patients were enrolled into the trial. Miltuximabwas well tolerated and did not elicit any drug-related adverse reactions. Liver and spleen uptake of 67Ga-Miltuximabwas observed from 30 min to 72 hours post dose. Pre-infusion of unlabelled Miltuximab resulted in reduced liver accumulation and increased distribution in the rest of the body. Miltuximab targeting to sites of active progressive disease was observed in certain prostate cancer patients who had failed enzalutamide treatment. Dosimetry analysis combined with antibody pharmacokinetic data was used to establish safe dose limits for a Phase 1 study. Conclusions: This study is the first in human for Miltuximaband demonstrates its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2019. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab. Clinical trial information: ACTRN12616000787482.


2009 ◽  
Vol 101 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Mohsen Jamali ◽  
Soroush G. Sadeghi ◽  
Kathleen E. Cullen

The distinction between sensory inputs that are a consequence of our own actions from those that result from changes in the external world is essential for perceptual stability and accurate motor control. In this study, we investigated whether linear translations are encoded similarly during active and passive translations by the otolith system. Vestibular nerve afferents innervating the saccule or utricle were recorded in alert macaques. Single unit responses were compared during passive whole body, passive head-on-body, and active head-on-body translations (vertical, fore-aft, or lateral) to assess the relative influence of neck proprioceptive and efference copy-related signals on translational coding. The response dynamics of utricular and saccular afferents were comparable and similarly encoded head translation during passive whole body versus head-on-body translations. Furthermore, when monkeys produced active head-on-body translations with comparable dynamics, the responses of both regular and irregular afferents remained comparable to those recorded during passive movements. Our findings refute the proposal that neck proprioceptive and/or efference copy inputs coded by the efferent system function to modulate the responses of the otolith afferents during active movements. We conclude that the vestibular periphery provides faithful information about linear movements of the head in the space coordinates, regardless of whether they are self- or externally generated.


1990 ◽  
Vol 64 (6) ◽  
pp. 1695-1703 ◽  
Author(s):  
V. J. Wilson ◽  
Y. Yamagata ◽  
B. J. Yates ◽  
R. H. Schor ◽  
S. Nonaka

1. To compare the properties of the vestibulocollic reflex (VCR) with those of vestibular neurons projecting to the neck [vestibulocollic (VC) neurons], we have studied the behavior of the latter in the decerebrate cat. Neurons were identified by their antidromic responses to stimulation in C1-C2, but not C5. Responses to stimulation of vestibular and neck receptors were produced by rotation of the body and head in vertical planes. 2. We determined the plane of whole body (vestibular) or body with head counter-rotated (neck) rotation, which produced the maximal modulation of each neuron (response vector orientation). Neuron dynamics were then studied with sinusoidal (0.02–2 Hz) stimuli aligned with this orientation. 3. On the basis of dynamics and vector orientation, the neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 4. The properties of this sample of VC neurons are similar to those of a larger population of vestibular neurons whose projection was not identified. For example, the distributions of cells with different types of vestibular inputs were roughly the same; in particular, few cells showed STC responses. In addition, there was no evidence of significant convergence of like canals across the midline (e.g., right anterior + left anterior). 5. Also similar to the larger unidentified population, 80% of VC neurons tested for neck input received such an input. The neck and vestibular responses tended to be antagonistic; the vector orientations were usually opposite, and the response gains and phases similar.(ABSTRACT TRUNCATED AT 250 WORDS)


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Jiaming Guo ◽  
Deyun Zhao ◽  
Xiao Lei ◽  
Hainan Zhao ◽  
Yanyong Yang ◽  
...  

Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects ofH2on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing thatH2could diminish the detriment induced by LDLTR and suggesting the protective efficacy ofH2in multiple systems in mice against LDLTR.


2011 ◽  
Vol 301 (5) ◽  
pp. R1380-R1390 ◽  
Author(s):  
Yoichiro Sugiyama ◽  
Takeshi Suzuki ◽  
Vincent J. DeStefino ◽  
Bill J. Yates

Anatomical studies have demonstrated that the vestibular nuclei project to nucleus tractus solitarius (NTS), but little is known about the effects of vestibular inputs on NTS neuronal activity. Furthermore, lesions of NTS abolish vomiting elicited by a variety of different triggering mechanisms, including vestibular stimulation, suggesting that emetic inputs may converge on the same NTS neurons. As such, an emetic stimulus that activates gastrointestinal (GI) receptors could alter the responses of NTS neurons to vestibular inputs. In the present study, we examined in decerebrate cats the responses of NTS neurons to rotations of the body in vertical planes before and after the intragastric administration of the emetic compound copper sulfate. The activity of more than one-third of NTS neurons was modulated by vertical vestibular stimulation, with most of the responsive cells having their firing rate altered by rotations in the head-up or head-down directions. These responses were aligned with head position in space, as opposed to the velocity of head movements. The activity of NTS neurons with baroreceptor, pulmonary, and GI inputs could be modulated by vertical plane rotations. However, injection of copper sulfate into the stomach did not alter the responses to vestibular stimulation of NTS neurons that received GI inputs, suggesting that the stimuli did not have additive effects. These findings show that the detection and processing of visceral inputs by NTS neurons can be altered in accordance with the direction of ongoing movements.


1986 ◽  
Vol 56 (3) ◽  
pp. 615-623 ◽  
Author(s):  
D. V. Muralidhara ◽  
P. S. Shetty

1. Nutritional deprivation was induced preweaning in Wistar rats by increasing the litter size to sixteen, while paired litters with only five pups served as controls. The nutritionally deprived pups were rehabilitated after weaning by ad lib. access to an adequate diet.2. The body-weights and body lengths were significantly lower in the nutritionally deprived group and significant differences persisted even after 9 weeks of rehabilitation.3. The body temperature of the nutritionally deprived animals was significantly lower than that of their paired controls, both before and following nutritional rehabilitation, except for a short period after weaning when the nutritionally deprived animals were initially given the diet ad lib.4. The resting oxygen consumption of the nutritionally deprived animals was comparable to that of the controls when corrected for metabolic body size, both before and after weaning. Noradrenaline-stimulated increase in 02 consumption (non-shivering thermogenesis; NST) was reduced by 50% at weaning in the nutritionally deprived animals and returned to levels comparable to those of controls within a short period of rehabilitation.5. The decrease in NST capacity seen in the nutritionally deprived animals was associated with an inability to thermoregulate when exposed to cold (5°), resulting in death. Cold-induced thermogenesis (CIT) also reappeared soon after nutritional rehabilitation.6. Reduction in metabolic rate, NST and CIT seen in the animals nutritionally deprived preweaning was short-lived and disappeared soon after nutritional rehabilitation. Rapid reversal of these physiological changes indicates that they do not confer any long-term benefit or change in metabolic efficiency and are unlike the changes in body size and growth which do not completely recover following nutritional rehabilitation.


2009 ◽  
Vol 101 (2) ◽  
pp. 988-1001 ◽  
Author(s):  
Soroush G. Sadeghi ◽  
Jay M. Goldberg ◽  
Lloyd B. Minor ◽  
Kathleen E. Cullen

The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320°/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (∼10 spikes/s) than in regular afferents (∼2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50° upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition.


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