scholarly journals Effects of Propofol and Ketamine on The Neural Oscillations in CA1 of Rat Intact Hippocampus

2020 ◽  
Author(s):  
Zhang Yu ◽  
Ping Chen ◽  
Zhi-yi Tu ◽  
Yi-heng Liu ◽  
Zhi-ru Wang ◽  
...  
Keyword(s):  
Field Potential ◽  
Inhibitory Effect ◽  
Neural Oscillations ◽  
General Anesthetics ◽  
Bath Application ◽  
Spectrum Intensity ◽  
Underlying Mechanisms ◽  
The Brain ◽  
Local Field Potential Lfp

Abstract In this study, in vitro intact hippocampal preparation model was utilized to observe the effects of propofol and ketamine on the neural oscillations in CA1 of rat hippocampus. The intact hippocampi were dissected from the brain tissues of rats aged 14-16 days postnatal. Local field potential (LFP) recordings were performed with propofol and ketamine bath application at different concentrations. The power spectrum intensity of LFP in all the frequency bands, including delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-80 Hz), were inhibited in a concentrationdependent manner by both general anesthetics. In order to further investigate the underlying mechanisms, the major binding site of propofol and ketamine were blocked respectively by picrotoxin and (2R)-amino-5-phosphonopentanoate when bath applying the general anesthetics. It revealed that the inhibitory effect of propofol on hippocampal oscillations might be via γ-aminobutyric acid A receptor, while the inhibitory effect of ketamine might be unconcerned with N-methyl-D-aspartic acid receptor.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

scholarly journals Scapinin-induced Inhibition of Axon Elongation Is Attenuated by Phosphorylation and Translocation to the Cytoplasm

2011 ◽  
Vol 286 (22) ◽  
pp. 19724-19734 ◽  
Author(s):  
Hovik Farghaian ◽  
Yu Chen ◽  
Ada W. Y. Fu ◽  
Amy K. Y. Fu ◽  
Jacque P. K. Ip ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Cortex ◽  
Inhibitory Effect ◽  
Adult Brain ◽  
Actin Binding ◽  
Mutant Form ◽  
Axon Elongation ◽  
Rat Cortical Neurons ◽  
The Brain

Scapinin is an actin- and PP1-binding protein that is exclusively expressed in the brain; however, its function in neurons has not been investigated. Here we show that expression of scapinin in primary rat cortical neurons inhibits axon elongation without affecting axon branching, dendritic outgrowth, or polarity. This inhibitory effect was dependent on its ability to bind actin because a mutant form that does not bind actin had no effect on axon elongation. Immunofluorescence analysis showed that scapinin is predominantly located in the distal axon shaft, cell body, and nucleus of neurons and displays a reciprocal staining pattern to phalloidin, consistent with previous reports that it binds actin monomers to inhibit polymerization. We show that scapinin is phosphorylated at a highly conserved site in the central region of the protein (Ser-277) by Cdk5 in vitro. Expression of a scapinin phospho-mimetic mutant (S277D) restored normal axon elongation without affecting actin binding. Instead, phosphorylated scapinin was sequestered in the cytoplasm of neurons and away from the axon. Because its expression is highest in relatively plastic regions of the adult brain (cortex, hippocampus), scapinin is a new regulator of neurite outgrowth and neuroplasticity in the brain.

Coherent Electrical Activity Between Vibrissa Sensory Areas of Cerebellum and Neocortex Is Enhanced During Free Whisking

2002 ◽  
Vol 87 (4) ◽  
pp. 2137-2148 ◽  
Author(s):  
Sean M. O'Connor ◽  
Rune W. Berg ◽  
David Kleinfeld
Keyword(s):  
Electrical Activity ◽  
Sensory Input ◽  
Field Potential ◽  
Sensory Cortex ◽  
Brain Areas ◽  
Low Coherence ◽  
Primary Sensory Cortex ◽  
High Level ◽  
The Brain ◽  
Local Field Potential Lfp

We tested if coherent signaling between the sensory vibrissa areas of cerebellum and neocortex in rats was enhanced as they whisked in air. Whisking was accompanied by 5- to 15-Hz oscillations in the mystatial electromyogram, a measure of vibrissa position, and by 5- to 20-Hz oscillations in the differentially recorded local field potential (∇LFP) within the vibrissa area of cerebellum and within the ∇LFP of primary sensory cortex. We observed that only 10% of the activity in either cerebellum or sensory neocortex was significantly phase-locked to rhythmic motion of the vibrissae; the extent of this modulation is in agreement with the results from previous single-unit measurements in sensory neocortex. In addition, we found that 40% of the activity in the vibrissa areas of cerebellum and neocortex was significantly coherent during periods of whisking. The relatively high level of coherence between these two brain areas, in comparison with their relatively low coherence with whisking per se, implies that the vibrissa areas of cerebellum and neocortex communicate in a manner that is incommensurate with whisking. To the extent that the vibrissa areas of cerebellum and neocortex communicate over the same frequency band as that used by whisking, these areas must multiplex electrical activity that is internal to the brain with activity that is that phase-locked to vibrissa sensory input.

scholarly journals SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi278-vi279
Author(s):  
Katayoun Ayasoufi ◽  
Christian K Pfaller ◽  
Roman H Khadka ◽  
Fang Jin ◽  
Jiaying Zheng ◽  
...  
Keyword(s):  
Brain Injury ◽  
T Cell ◽  
Thymic Involution ◽  
Systemic Immunosuppression ◽  
Cell Counts ◽  
Immune Deficiencies ◽  
Underlying Mechanisms ◽  
Neurological Injuries ◽  
The Brain

Abstract Systemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma (GBM) causes mortality and leads to failure of immune-modulating therapies. Exact immunological nature and the underlying mechanisms of this immunosuppression are unknown. Our goal was to define effects of neurological insults given exclusively to the brain on the thymus. The thymus is the primary immune organ responsible for T-cell development and maintenance both in children and in adults. We evaluated the brain-thymus communication using the following neurological insults: physical injury, CNS viral infection, sterile injury, tumor implantation, and seizures. All insults resulted in significant thymic involution that was reversible upon clearance of the insult. Thymic involution did not occur following similar peripheral insults. We next demonstrated that the GL261 model of GBM recapitulates hallmark features of peripheral immunosuppression observed in GBM patients including low CD4 T-cell counts. Thus, we aimed to further study the immunosuppression affecting the thymus in this clinically relevant model. Principle component analysis following RNA-sequencing of thymi from naïve and glioma-bearing mice revealed unbiased separation of the groups suggesting that the thymus is directly affected by a brain tumor. To determine the extent to which thymic involution was caused by a soluble factor we employed parabiosis. We demonstrated that thymic involution was transferable from glioma-bearing to non-tumor-bearing parabionts. Similarly, serum taken from GL261 glioma-bearing mice potently inhibited proliferation of T-cells in vitro. Together our data demonstrate that CNS-specific insults, regardless of nature, cause immunosuppression by prompting thymic involution through circulating factors. This accounts at least partially for immune deficiencies observed following neurological injuries. Identification of this suppressive factor is crucial in designing future therapeutics for GBM patients, and patients with other acute and chronic neurological trauma.

BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 1. THE EFFECT OF CHLORPROMAZINE ON RESPIRATORY ACTIVITY OF ISOLATED RAT BRAIN CORTEX

1957 ◽  
Vol 35 (12) ◽  
pp. 1135-1144 ◽  
Author(s):  
O. Lindan ◽  
J. H. Quastel ◽  
S. Sved
Keyword(s):  
Plasma Proteins ◽  
Brain Cortex ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Acid Dyes ◽  
Highly Sensitive ◽  
Binding Power ◽  
The Brain

Chlorpromazine exerts a progressive inhibitory activity (at 0.3–0.6 mM) on the respiration of brain cortex in presence of either glucose, fructose, pyruvate, or L-glutamate. A similar progressive inhibition occurs with other phenothiazine derivatives such as methylene blue and phenergan. However, chlorpromazine does not inhibit oxygen uptake in the presence of succinate. Potassium-stimulated respiration is highly sensitive to chlorpromazine, as it is markedly diminished by 0.2 mM concentration of the drug, a concentration which does not affect the unstimulated respiration. The increased inhibition of potassium-stimulated respiration is only clearly seen during the early part of the experiment.Chlorpromazine is bound by tissue constituents. At a constant concentration of chlorpromazine (0.6 mM), its inhibitory effect on cortical respiration may be abolished by markedly increasing the amount of tissue present. The inhibitory effect of chlorpromazine may be diminished by addition of plasma proteins (αβ-globulin) or by addition of heated homogenized brain, liver, or kidney. No binding occurs with polyglutamic acid, ribonucleic, and deoxyribonucleic acids, but binding does occur with certain acid dyes such as trypan red. Trypan red may be used to immobilize free chlorpromazine. When the latter drug is absorbed, however, by the nervous tissue, the addition of trypan red has no effect on the metabolic inhibitions brought about by the absorbed chlorpromazine.It is concluded that chlorpromazine resembles a large variety of narcotics and anaesthetics in its marked inhibitory effects on potassium-stimulated respiration of the brain. Its action, in vitro, however, differs from that of the narcotics in bringing about progressive, apparently irreversible, inhibitions and in its high binding power with tissue proteins. Such apparently irreversible inhibition is consistent with the conclusion that the drug, after combination with the tissue, gradually diffuses into the cell bringing about metabolic inhibitions.

Inflammation Increases Neuronal Sensitivity to General Anesthetics

2016 ◽  
Vol 124 (2) ◽  
pp. 417-427 ◽  
Author(s):  
Sinziana Avramescu ◽  
Dian-Shi Wang ◽  
Irene Lecker ◽  
William T. H. To ◽  
Antonello Penna ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Cortical Neurons ◽  
Receptor Activity ◽  
Aminobutyric Acid ◽  
General Anesthetics ◽  
Enhanced Sensitivity ◽  
Behavioral Sensitivity ◽  
Underlying Mechanisms

Abstract Background Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of γ-aminobutyric acid type A (GABAA) receptors expressed on the surface of neurons, which supports the hypothesis that inflammation increases up-regulation of GABAA receptor activity by anesthetics, thereby enhancing the behavioral sensitivity to these drugs. Methods To mimic inflammation in vitro, cultured hippocampal and cortical neurons were pretreated with interleukin (IL)-1β. Whole cell patch clamp methods were used to record currents evoked by γ-aminobutyric acid (GABA) (0.5 μM) in the absence and presence of etomidate or isoflurane. To mimic inflammation in vivo, mice were treated with lipopolysaccharide, and several anesthetic-related behavioral endpoints were examined. Results IL-1β increased the amplitude of current evoked by GABA in combination with clinically relevant concentrations of either etomidate (3 μM) or isoflurane (250 μM) (n = 5 to 17, P &lt; 0.05). Concentration–response plots for etomidate and isoflurane showed that IL-1β increased the maximal current 3.3-fold (n = 5 to 9) and 1.5-fold (n = 8 to 11), respectively (P &lt; 0.05 for both), whereas the half-maximal effective concentrations were unchanged. Lipopolysaccharide enhanced the hypnotic properties of both etomidate and isoflurane. The immobilizing properties of etomidate, but not isoflurane, were also increased by lipopolysaccharide. Both lipopolysaccharide and etomidate impaired contextual fear memory. Conclusions These results provide proof-of-concept evidence that inflammation increases the sensitivity of neurons to general anesthetics. This increase in anesthetic up-regulation of GABAA receptor activity in vitro correlates with enhanced sensitivity for GABAA receptor–dependent behavioral endpoints in vivo.

Kanamycin Inhibits Cochlear-Renal ODC in Neonatal Rats

1992 ◽  
Vol 107 (4) ◽  
pp. 501-510 ◽  
Author(s):  
Andrew T. Lyos ◽  
William E. Winter ◽  
Charles M. Henley
Keyword(s):  
Organ Of Corti ◽  
Lateral Wall ◽  
Inhibitory Effect ◽  
Polyamine Biosynthesis ◽  
Key Enzyme ◽  
Old Rats ◽  
In Vivo Effects ◽  
The Brain

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is important in development and regeneration. We hypothesize that aminoglycoside inhibition of ODC mediates developmental hypersensitivity to aminoglycoside ototoxicity. Kanamycin effects on ODC activity (decarboxylation of ornithine) in vitro were determined in the postmitochondriai fraction of cochlear and renal homogenates from 11-day-old rats. Kanamycin inhibited cochlear and renal ODC by an uncompetitive mechanism. For the cochlear enzyme, the inhibitor constant (Ki) for kanamycin was 99 ± 25 (μmol/L; for the renal enzyme, the Ki = 1.5 ± 0.1 mmol/L. In vivo effects of kanamycin on cochlear, renal, brain ODC activity were determined in rats treated with kanamycin (400 mg/kg/day, intramuscularly) or saline during postnatal days 11 through 20, the hypersensitive period for ototoxicity. Rats were killed on postnatal days 12,14,16, and 20 and ODC was assayed. Kanamycin significantly inhibited ODC in the lateral wall-organ of Corti and kidney (ANOVA α = 0.05), but had no effect on cochlear nerve and no consistent inhibitory effect in the brain. These results suggest that ODC is a potential target of kanamycin in susceptible tissues and may be a contributing factor in developmental sensitivity to the drug by inhibiting repair and developmental processes mediated by ODC.

scholarly journals Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.

2004 ◽  
Vol 51 (1) ◽  
pp. 207-212 ◽  
Author(s):  
Anna Barańczyk-Kuźma ◽  
Magdalena Kuźma ◽  
Marzena Gutowicz ◽  
Beata Kaźmierczak ◽  
Jacek Sawicki
Keyword(s):  
Human Brain ◽  
Tricyclic Antidepressants ◽  
Inhibitory Effect ◽  
Glutathione S Transferase ◽  
Brain Localization ◽  
Vitro Effect ◽  
Derivatives Of ◽  
The Brain ◽  
Noncompetitive Inhibitors

GST pi, the main glutathione S-transferase isoform present in the human brain, was isolated from various regions of the brain and the in vitro effect of tricyclic antidepressants on its activity was studied. The results indicated that amitripyline and doxepin--derivatives of dibenzcycloheptadiene, as well as imipramine and clomipramine--derivatives of dibenzazepine, inhibit the activity of GST pi from frontal and parietal cortex, hippocampus and brain stem. All these tricyclics are noncompetitive inhibitors of the enzyme with respect to reduced glutathione and noncompetitive (amitripyline, doxepin) or uncompetitive (imipramine, clomipramine) with respect to the electrophilic substrate. Their inhibitory effect is reversible and it depends on the chemical structure of the tricyclic antidepressants rather than on the brain localization of the enzyme. We conclude that the interaction between GST pi and the drugs may reduce their availability in the brain and thus affect their therapeutic activity. On the other hand, tricyclic antidepressants may decrease the efficiency of the enzymatic barrier formed by GST and increase the exposure of brain to toxic electrophiles. Reactive electrophiles not inactivated by GST may contribute in adverse effects caused by these drugs.

scholarly journals Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking ROS/NF-κB/NLRP3 Axis in Macrophages

2021 ◽  
Vol 11 ◽  
Author(s):  
Yufei Luo ◽  
Bojun Xiong ◽  
Haiping Liu ◽  
Zehong Chen ◽  
Huihui Huang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Inhibitory Effect ◽  
Receptor Protein ◽  
Mechanistic Study ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Underlying Mechanisms

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.

scholarly journals Effect of amplitude correlations on coherence in the local field potential

2014 ◽  
Vol 112 (4) ◽  
pp. 741-751 ◽  
Author(s):  
Ramanujan Srinath ◽  
Supratim Ray
Keyword(s):  
Local Field ◽  
Local Field Potential ◽  
Multiple Scales ◽  
Field Potential ◽  
Interelectrode Distance ◽  
Study Phase ◽  
Temporal Correlations ◽  
Two Factors ◽  
The Brain ◽  
Local Field Potential Lfp

Neural activity across the brain shows both spatial and temporal correlations at multiple scales, and understanding these correlations is a key step toward understanding cortical processing. Correlation in the local field potential (LFP) recorded from two brain areas is often characterized by computing the coherence, which is generally taken to reflect the degree of phase consistency across trials between two sites. Coherence, however, depends on two factors—phase consistency as well as amplitude covariation across trials—but the spatial structure of amplitude correlations across sites and its contribution to coherence are not well characterized. We recorded LFP from an array of microelectrodes chronically implanted in the primary visual cortex of monkeys and studied correlations in amplitude across electrodes as a function of interelectrode distance. We found that amplitude correlations showed a similar trend as coherence as a function of frequency and interelectrode distance. Importantly, even when phases were completely randomized between two electrodes, amplitude correlations introduced significant coherence. To quantify the contributions of phase consistency and amplitude correlations to coherence, we simulated pairs of sinusoids with varying phase consistency and amplitude correlations. These simulations confirmed that amplitude correlations can significantly bias coherence measurements, resulting in either over- or underestimation of true phase coherence. Our results highlight the importance of accounting for the correlations in amplitude while using coherence to study phase relationships across sites and frequencies.

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