scholarly journals Reduced motoneuron excitability in a rat model of sepsis

2013 ◽  
Vol 109 (7) ◽  
pp. 1775-1781 ◽  
Author(s):  
Paul Nardelli ◽  
Jaffar Khan ◽  
Randall Powers ◽  
Tim C. Cope ◽  
Mark M. Rich

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW.

Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.


2017 ◽  
Vol 58 (6) ◽  
pp. 881-886 ◽  
Author(s):  
Michiyo Suzuki ◽  
Yuya Hattori ◽  
Tetsuya Sakashita ◽  
Yuichiro Yokota ◽  
Yasuhiko Kobayashi ◽  
...  

Abstract Radiation may affect essential functions and behaviors such as locomotion, feeding, learning and memory. Although whole-body irradiation has been shown to reduce motility in the nematode Caenorhabditis elegans, the detailed mechanism responsible for this effect remains unknown. Targeted irradiation of the nerve ring responsible for sensory integration and information processing would allow us to determine whether the reduction of motility following whole-body irradiation reflects effects on the central nervous system or on the muscle cells themselves. We therefore addressed this issue using a collimating microbeam system. However, radiation targeting requires the animal to be immobilized, and previous studies have anesthetized animals to prevent their movement, thus making it impossible to assess their locomotion immediately after irradiation. We developed a method in which the animal was enclosed in a straight, microfluidic channel in a polydimethylsiloxane chip to inhibit free motion during irradiation, thus allowing locomotion to be observed immediately after irradiation. The head region (including the central nervous system), mid region around the intestine and uterus, and tail region were targeted independently. Each region was irradiated with 12 000 carbon ions (12C; 18.3 MeV/u; linear energy transfer = 106.4 keV/μm), corresponding to 500 Gy at a φ20 μm region. Motility was significantly decreased by whole-body irradiation, but not by irradiation of any of the individual regions, including the central nervous system. This suggests that radiation inhibits locomotion by a whole-body mechanism, potentially involving motoneurons and/or body-wall muscle cells, rather than affecting motor control via the central nervous system and the stimulation response.


1975 ◽  
Vol 38 (5) ◽  
pp. 285-300 ◽  
Author(s):  
A. G. HUGUNIN ◽  
R. L. BRADLEY

Mercury is naturally concentrated in geographical belts, but geological cycling has distributed the element in all strata of the earth. Natural concentrations of mercury are approximately 100 ppb in soil, 0.06 ppb in fresh water, 0.01–0.30 ppb in sea water, and 0.003–0.009 μg/m3 in air. Concentrations vary, being highest near mineral deposits. The concentration of mercury in some areas has been significantly increased by human carelessness. An epidemic among Japanese fishing families, death of Swedish wildlife, and discovery of elevated mercury levels in American fish focused attention on this problem. The discovery that certain species are capable of methylating inorganic mercury indicates pollution with any chemical form of mercury is dangerous. Alkylmercurials are the most dangerous form of mercury in the environment. Alkylmercurials are absorbed from the gastrointestinal tract, diffuse across the blood-brain carrier, and pass through the placental membrane in significantly higher proportions than other mercury compounds. The whole body half-life of methyl mercury in humans is 76 ± 3 days compared to half-lives of 37 ± 3 days for men and 48 ± 5 days for women observed for mercuric salts. Not readily broken down, sufficient concentrations of methyl mercury can cause irreversible damage to the central nervous system. Renal damage usually results from high levels of aryl- or alkoxyalkylmercurials and inorganic mercury; however, vapors of elemented mercury can damage the central nervous system. Organic mercury compounds cause chromosome changes, but the medical implications resulting from levels of mercury in food are unknown. The concentration of mercury in red blood cells and hair is indicative of the exposure to alkylmercurials. On a group basis, blood and urine concentrations of mercury may corrrelate with recent exposure to mercury.


1975 ◽  
Vol 63 (3) ◽  
pp. 801-811
Author(s):  
M. V. Thomas ◽  
J. E. Treherne

Simultaneous intracellular and sucrose-gap recordings showed, in contrast to previous findings, that the electrical parameters of giant axons were similar to intact and desheathed connectives bathed with the ‘extracellular Ringer’ of Yamasaki & Narahashi. This implies that the extra-axonal sodium concentration, in situ, is likely to be lower than had been previously supposed. Axonal responses showed that, despite the high blood concentration of 24–2 mM-K+ measured by flame photometry, the effective concentration in the blood was 10–15 mM-K+ which corresponds to the measurements made with potassium-selective electrodes. The activity of the blood potassium ions caused a marked reduction in the amplitude of the action potentials following surgical desheathing or disruption of the blood-brain barrier with hypertonic urea. It is suggested that a regulatory mechanism exists in the central nervous system which counteracts the effects of the high blood potassium level.


2018 ◽  
Vol 125 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
A. Del Vecchio ◽  
A. Úbeda ◽  
M. Sartori ◽  
J. M. Azorín ◽  
F. Felici ◽  
...  

Force is generated by muscle units according to the neural activation sent by motor neurons. The motor unit is therefore the interface between the neural coding of movement and the musculotendinous system. Here we propose a method to accurately measure the latency between an estimate of the neural drive to muscle and force. Furthermore, we systematically investigate this latency, which we refer to as the neuromechanical delay (NMD), as a function of the rate of force generation. In two experimental sessions, eight men performed isometric finger abduction and ankle dorsiflexion sinusoidal contractions at three frequencies and peak-to-peak amplitudes {0.5, 1, and 1.5 Hz; 1, 5, and 10 of maximal force [%maximal voluntary contraction (MVC)]}, with a mean force of 10% MVC. The discharge timings of motor units of the first dorsal interosseous (FDI) and tibialis anterior (TA) muscle were identified by high-density surface EMG decomposition. The neural drive was estimated as the cumulative discharge timings of the identified motor units. The neural drive predicted 80 ± 0.4% of the force fluctuations and consistently anticipated force by 194.6 ± 55 ms (average across conditions and muscles). The NMD decreased nonlinearly with the rate of force generation ( R2 = 0.82 ± 0.07; exponential fitting) with a broad range of values (from 70 to 385 ms) and was 66 ± 0.01 ms shorter for the FDI than TA ( P < 0.001). In conclusion, we provided a method to estimate the delay between the neural control and force generation, and we showed that this delay is muscle-dependent and is modulated within a wide range by the central nervous system. NEW & NOTEWORTHY The motor unit is a neuromechanical interface that converts neural signals into mechanical force with a delay determined by neural and peripheral properties. Classically, this delay has been assessed from the muscle resting level or during electrically elicited contractions. In the present study, we introduce the neuromechanical delay as the latency between the neural drive to muscle and force during variable-force contractions, and we show that it is broadly modulated by the central nervous system.


2019 ◽  
Vol 41 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Camilla Scheele ◽  
Christian Wolfrum

Abstract Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX – XXX, 2020)


Author(s):  
Anna Lena Fisse ◽  
Kalliopi Pitarokoili ◽  
David Leppert ◽  
Jeremias Motte ◽  
Xiomara Pedreiturria ◽  
...  

Abstract Objective Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. Methods Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. Results NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). Conclusion NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.


Author(s):  
R. M. Williamson ◽  
B. L. Roberts

Whole body cooling of dogfish initially anaesthetized with MS 222 produced total immobility and permitted prolonged surgical procedures. Additional anaesthesia was not required, and on rewarming recovery was rapid.Electromyographic recordings of jaw-closing and fin-elevating reflexes of the dogfish during body cooling indicated that processes within the central nervous system were being blocked and that the effect was most pronounced on polysynaptic reflexes.


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