Focal warming in the nucleus of the solitary tract prolongs the laryngeal chemoreflex in decerebrate piglets

2007 ◽  
Vol 102 (1) ◽  
pp. 54-62 ◽  
Author(s):  
L. Xia ◽  
T. A. Damon ◽  
J. C. Leiter ◽  
D. Bartlett
Keyword(s):  
Brain Stem ◽  
Brain Tissue ◽  
Rectal Temperature ◽  
Respiratory Activity ◽  
Nucleus Ambiguus ◽  
Tissue Temperature ◽  
Whole Body ◽  
Solitary Tract ◽  
Neonatal Piglets ◽  
The Brain

The laryngeal chemoreflex (LCR), elicited by a drop of water in the larynx, is exaggerated by mild hyperthermia (body temperature = 40–41°C) in neonatal piglets. We tested the hypothesis that thermal prolongation of the LCR results from heating the nucleus of the solitary tract (NTS), where laryngeal afferents first form synapses in the brain stem. Three- to 13-day-old piglets were decerebrated and vagotomized and studied without anesthesia while paralyzed and ventilated. Phrenic nerve activity and rectal temperature were recorded. A thermode was placed in the medulla, and the brain tissue temperature was recorded with a thermistor ∼1 mm from the tip of the thermode. When the thermode was inserted into the brain stem, respiratory activity was arrested or greatly distorted in eight animals. However, the thermode was inserted in nine animals without disrupting respiratory activity, and in these animals, warming the medullary thermode (thermistor temperature = 40–41°C) while holding rectal temperature constant reversibly exaggerated the LCR. The caudal raphé was warmed focally by ∼2°C in four additional animals; this did not alter the duration of the LCR in these animals. Thermodes placed in the NTS did not disrupt respiratory activity, but they did prolong the LCR when warmed. Thermodes that were placed deep to the NTS in the region of the nucleus ambiguus disrupted respiratory activity, which precluded any analysis of the LCR. We conclude that prolongation of the laryngeal chemoreflex by whole body hyperthermia originates from the elevation of brain tissue temperature within in the NTS.

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 P11.62 Brain distribution models to select polymer-delivered drugs for the intra-cavity treatment of malignant glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii58-iii58
Author(s):  
J Rowlinson ◽  
P McCrorie ◽  
S Smith ◽  
D Barrett ◽  
D Kim ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Brain Homogenate ◽  
Systemic Toxicity ◽  
The Body ◽  
Whole Body ◽  
Label Free ◽  
In Vivo Models ◽  
Franz Cell ◽  
Diffusion Rates ◽  
The Brain

Abstract BACKGROUND Conventional oral or intravenous chemotherapy distributes drugs to the whole body whereby systemic toxicity to healthy parts of the body (e.g. bone marrow failure) limits the maximum dose that can be achieved in the brain. This presents a particular concern for CNS tumours where the blood-brain-barrier (BBB) restricts drug influx from the circulation. The ability to deliver chemotherapy locally at the tumour site offers the opportunity to target residual cancer cells post-surgery whilst minimising systemic toxicity. We have developed a poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) polymer matrix that forms a porous paste at room temperature when mixed with chemotherapy-containing saline, solidifying only at body temperature, with close apposition to the irregular surgical cavity. It is important that we can observe whether the drugs released from PLGA/PEG can penetrate brain parenchyma beyond the surgical resection margin at therapeutic doses. Currently the only way to measure the distribution of drugs in the body is to inject radioactive drugs into an animal. We aim to establish drug distribution parameters using label-free mass spectrometry imaging methods, prior to selection of drug formulations for clinically-relevant in vivo models. Drugs that penetrate the brain the furthest will be identified as good candidates for localised brain cancer drug delivery using PLGA/PEG paste. MATERIAL AND METHODS Diffusion rates were measured by examining the proportion of olaparib, dasatnib, carboplatin, etoposide, paclitaxel and gemcitabine at 2mg/ml concentration, which passes through 1mm slices of rat brain tissue within Franz cell chambers over a 6 hour period. The spatio-temporal distribution of label-free olaparib and dasatinib within mouse brain homogenate was quantitatively measured using innovative 3D OrbiSIMS, a hybrid time-of-flight / OrbitrapTM secondary ion mass spectrometer. RESULTS Within the Franz cell model, carboplatin and gemcitabine showed the highest diffusion rate diffusion at 16.4 and 6.53 µg/cm2/h respectively whereas olaparib, etoposide and paclitaxel were relatively poorly diffused at 1.87, 3.82 and 2.27 µg/cm2/h respectively. The minimum threshold of OrbiSIMS detection for label-free olaparib and dasatinib ions was 0.025 mg/ml and 0.2 mg/ml respectively throughout brain homogenate. CONCLUSION This study demonstrates different diffusion rates through brain tissue, between label-free chemotherapy drugs of distinct chemistries, with highest diffusion rates observed for carboplatin and gemcitabine. We also demonstrate label-free detection of olaparib and dasatinib using the innovative 3D OrbiSIMS method. These models will facilitate the rapid identification of agents most amenable for localised biomaterial-based chemotherapy delivery with high brain penetrance.

Bidirectional Electrical Coupling Between Inspiratory Motoneurons in the Newborn Mouse Nucleus Ambiguus

1997 ◽  
Vol 78 (6) ◽  
pp. 3508-3510 ◽  
Author(s):  
Jens C. Rekling ◽  
Jack L. Feldman
Keyword(s):  
Brain Stem ◽  
Impulse Activity ◽  
Electrical Coupling ◽  
Postnatal Period ◽  
The Other ◽  
Nucleus Ambiguus ◽  
Newborn Mouse ◽  
Coupling Ratio ◽  
Newborn Mice ◽  
The Brain

Rekling, Jens C. and Jack L. Feldman. Bidirectional electrical coupling between inspiratory motoneurons in the newborn mouse nucleus ambiguus. J. Neurophysiol. 78: 3508–3510, 1997. Some spinal and brain stem motoneurons are electrically coupled in the early postnatal period. To test whether respiratory motoneurons in the brain stem are electrically coupled, we performed single and dual whole cell patch recordings from presumptive motoneurons in the nucleus ambiguus in a rhythmically active brain stem slice from newborn mice. Two of eight (25%) biocytin-injected neurons showed dye-coupling and 4 of 11 (36%) of intracellularly recorded pairs of neurons showed evidence of bidirectional electrical coupling. Impulse activity in one cell elicited small spikelets in the other and hyperpolarization of one cell led to hyperpolarization of the other with a coupling ratio (Δ V 2:Δ V 1) of 0.03–0.14. We conclude that inspiratory ambiguus motoneurons in the newborn mouse brain stem are bidirectionally electrically coupled, which may serve to transmit or coordinate signals, chemical or electrical.

Genesis of rhythmic respiratory activity in pons independent of medulla

1985 ◽  
Vol 59 (3) ◽  
pp. 684-690 ◽  
Author(s):  
W. M. St John ◽  
T. A. Bledsoe
Keyword(s):  
Brain Stem ◽  
Phrenic Nerve ◽  
Respiratory Activity ◽  
Respiratory Rhythm ◽  
Related Activity ◽  
Pharmacological Agents ◽  
Pneumotaxic Center ◽  
Trigeminal Nerves ◽  
The Brain ◽  
Pontomedullary Junction

We hypothesized that rhythmic respiratory-related activity could be generated in pons independent of medullary mechanisms. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, we recorded efferent activities of the phrenic nerve and mylohyoid branch of the trigeminal nerve. Following transections of the brain stem at the pontomedullary junction, the phrenic and trigeminal nerves discharged with independent rhythms. Spontaneous trigeminal discharges eventually ceased but were reestablished after strychnine, doxapram, and/or protriptyline were administered. In some animals having no spontaneous trigeminal discharges after transection, these discharges appeared, with a rhythm different from the phrenic, following administration of these agents. In other cats having no transections between pons and medulla, these pharmacological agents induced trigeminal and phrenic discharges after kainic acid had been injected into the entire dorsal and ventral medullary respiratory nuclei. Phrenic and trigeminal discharges were linked, indicating survival of bulbospinal neurons or presence of pontospinal units. We conclude that rhythms, similar to respiratory rhythm, can occur by mechanisms in isolated pons. Such mechanisms are hypothesized to be within the pneumotaxic center and may underlie the neurogenesis of eupnea.

Allopregnanolone Effects on Transmission in the Brain Stem Solitary Tract Nucleus (NTS)

Neuroscience ◽  
2018 ◽  
Vol 379 ◽  
pp. 219-227 ◽  
Author(s):  
Sojin Kim ◽  
Sung-Moon Kim ◽  
Bermseok Oh ◽  
Jihoon Tak ◽  
Eunhee Yang ◽  
...  
Keyword(s):  
Brain Stem ◽  
Solitary Tract Nucleus ◽  
Solitary Tract ◽  
The Brain

Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia

1996 ◽  
Vol 81 (4) ◽  
pp. 1772-1777 ◽  
Author(s):  
J. C. Lamanna ◽  
M. A. Haxhiu ◽  
K. L. Kutina-Nelson ◽  
S. Pundik ◽  
B. Erokwu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Brain Stem ◽  
Respiratory Depression ◽  
Intracellular Ph ◽  
Metabolic Changes ◽  
Nucleus Ambiguus ◽  
Electromyographic Activity ◽  
Respiratory Drive ◽  
Energy Deficiency ◽  
The Brain

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772–1777, 1996.—Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized rats resulted in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within 11 min (range 5–27 min), presumably via central depressant mechanisms. At that time, the brain stems were frozen in situ for metabolic analyses. By using 20-μm lyophilized sections from frozen-fixed brain stem, microregional analyses of ATP, phosphocreatine, lactate, and intracellular pH were made from 1) the ventral portion of the nucleus gigantocellularis and the parapyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) the spinal trigeminal nucleus. At the time of respiratory depression, lactate was elevated threefold in all regions. Both ATP and phosphocreatine were decreased to 50 and 25% of control, respectively. Intracellular pH was more acidic by 0.2–0.4 unit in these regions but was relatively preserved in the chemosensitive regions near the ventral and dorsal medullary surfaces. These results show that hypoxia-induced respiratory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it appears that there was significant energy deficiency in the brain stem after hypoxia-induced respiratory depression had occurred.

Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods

2003 ◽  
Vol 95 (6) ◽  
pp. 2285-2291 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley
Keyword(s):  
Brain Stem ◽  
Cytochrome Oxidase ◽  
Vestibular Nucleus ◽  
Glycine Receptor ◽  
Nucleus Ambiguus ◽  
Medial Vestibular Nucleus ◽  
Hypoglossal Nucleus ◽  
Motor Nucleus ◽  
Sensitive Periods ◽  
The Brain

Previously, we reported that cytochrome oxidase (CO) activity in the rat pre-Bötzinger complex (PBC) exhibited a plateau on postnatal days (P) 3–4 and a prominent decrease on P12 (Liu and Wong-Riley, J Appl Physiol 92: 923–934, 2002). These changes were correlated with a concomitant reduction in the expression of glutamate and N-methyl-d-aspartate receptor subunit 1 and an increase in GABA, GABAB, glycine receptor, and glutamate receptor 2. To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe). Results indicated that, in all of the brain stem nuclei examined, CO activity exhibited a general increase with age from P0 to P21, with MVe having the slowest rise. Notably, in all of the nuclei examined except for MVe, there was a plateau or decrease at P3–P4 and a prominent rise-fall-rise pattern at P11–P13, similar to that observed in the PBC. In addition, there was a fall-rise-fall pattern at P15–P17 in these nuclei, instead of a plateau pattern in the PBC. Our data suggest that the two postnatal periods with reduced CO activity, P3–P4 and especially P12, may represent common sensitive periods for most of the brain stem nuclei with known or suspected respiratory control functions.

scholarly journals Neuromediator systems in some brain regions of rats subjected to morphine intoxication

2010 ◽  
Vol 56 (5) ◽  
pp. 562-569
Author(s):  
S.V. Lelevich ◽  
A.A. Novokshonov
Keyword(s):  
Brain Stem ◽  
Brain Tissue ◽  
Brain Regions ◽  
Cerebral Hemispheres ◽  
Serotonin Level ◽  
Chronic Morphine ◽  
Chronic Morphine Intoxication ◽  
System Functioning ◽  
Gaba Content ◽  
The Brain

The content of neuromediators and its metabolites in the cortex of cerebral hemispheres, in thalamus and brain stem was studied under chronic morphine intoxication (7-21 days). The morphine intake during 7-14 days was accompanied by changes of catecholamine system functioning, which was the most pronounced in the thalamus and the brain stem. These changes included increased secretion of dophamine and noradrenaline, their decrease in the brain tissue, and the increased content of their metabolites. The changes of serotonin and GABA content were less pronounced and included a decrease of serotonin level and the increase of the GABA content in different periods of narcotization.

Regional Quantification of Brain Tissue Strain Using Displacement-Encoding With Stimulated Echoes Magnetic Resonance Imaging

2018 ◽  
Vol 140 (8) ◽  
Author(s):  
Soroush Heidari Pahlavian ◽  
John Oshinski ◽  
Xiaodong Zhong ◽  
Francis Loth ◽  
Rouzbeh Amini
Keyword(s):  
Magnetic Resonance Imaging ◽  
Corpus Callosum ◽  
Brain Stem ◽  
Brain Tissue ◽  
Neural Tissue ◽  
Resonance Imaging ◽  
Tissue Strain ◽  
The Brain ◽  
Tissue Motion ◽  
Principal Strains

Intrinsic cardiac-induced deformation of brain tissue is thought to be important in the pathophysiology of various neurological disorders. In this study, we evaluated the feasibility of utilizing displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) to quantify two-dimensional (2D) neural tissue strain using cardiac-driven brain pulsations. We examined eight adult healthy volunteers with an electrocardiogram-gated spiral DENSE sequence performed at the midsagittal plane on a 3 Tesla MRI scanner. Displacement, pixel-wise trajectories, and principal strains were determined in seven regions of interest (ROI): the brain stem, cerebellum, corpus callosum, and four cerebral lobes. Quantification of small neural tissue motion and strain along with their spatial and temporal variations in different brain regions was found to be feasible using DENSE. The medial and inferior brain structures (brain stem, cerebellum, and corpus callosum) had significantly larger motion and strain compared to structures located more peripherally. The brain stem had the largest peak mean displacement (PMD) (187 ± 50 μm, mean ± SD). The largest mean principal strains in compression and extension were observed in the brain stem (0.38 ± 0.08%) and the corpus callosum (0.37 ± 0.08%), respectively. Measured values in percent strain were altered by as much as 0.1 between repeated scans. This study showed that DENSE can quantify regional variations in brain tissue motion and strain and has the potential to be utilized as a tool to evaluate the changes in brain tissue dynamics resulting from alterations in biomechanical stresses and tissue properties.

Sign in / Sign up

Export Citation Format

Share Document