Thalamic Locus Mediates Hypoxic Inhibition of Breathing in Fetal Sheep

1998 ◽  
Vol 79 (5) ◽  
pp. 2383-2393 ◽  
Author(s):  
Brian J. Koos ◽  
Andrew Chau ◽  
Masahiko Matsuura ◽  
Oscar Punla ◽  
Lawrence Kruger
Keyword(s):  
Brain Stem ◽  
Ibotenic Acid ◽  
Nuclear Region ◽  
Fetal Sheep ◽  
Nuclear Complex ◽  
Fetal Breathing ◽  
The Brain

Koos, Brian J., Andrew Chau, Masahiko Matsuura, Oscar Punla, and Lawrence Kruger. Thalamic locus mediates hypoxic inhibition of breathing in fetal sheep. J. Neurophysiol. 79: 2383–2393, 1998. The effects of lesions rostral to the brain stem on breathing responses to hypoxia were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the diencephalon is involved in hypoxic inhibition of fetal breathing. As in normal fetuses, hypoxia inhibited breathing with transection rostral to the thalamus or transection resulting in virtual destruction of the thalamus but sparing most of the parafascicular nuclear complex. Neuronal lesions were produced in the fetal diencephalon by injecting ibotenic acid through cannulas implanted in the brain. Hypoxic inhibition of breathing was abolished when the lesions encompassed the parafascicular nuclear complex but was retained when the lesions spared the parafascicular nuclear region or when the vehicle alone was injected. A new locus has been identified immediately rostral to the midbrain, which is crucial to hypoxic inhibition of fetal breathing. This thalamic sector involves the parafascicular nuclear complex and may link central O2-sensing cells to motoneurons that inhibit breathing.

Thalamic lesions dissociate breathing inhibition by hypoxia and adenosine in fetal sheep

2000 ◽  
Vol 278 (4) ◽  
pp. R831-R837 ◽  
Author(s):  
Brian J. Koos ◽  
Andrew Chau ◽  
Masahiko Matsuura ◽  
Oscar Punla ◽  
Lawrence Kruger
Keyword(s):  
Ibotenic Acid ◽  
Inhibitory Effects ◽  
Fetal Sheep ◽  
Breathing Control ◽  
Nuclear Complex ◽  
Fetal Breathing ◽  
Thalamic Lesions ◽  
Respiratory Responses

The effects of diencephalic lesions on respiratory responses to intra-arterially infused adenosine (ADO) were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the inhibitory effects of ADO on fetal breathing, like those of hypoxia, are mediated by the parafascicular nuclear complex (Pf) of the posteromedial thalamus. ADO inhibited breathing [control (C): 26 ± 2.6, ADO: 4 ± 1 min/h] in normal fetuses and in a fetus with a lesion that virtually destroyed the thalamus but left intact most of Pf. Neuronal lesions in the diencephalon, produced by injecting ibotenic acid, abolished the inhibitory effects of ADO on breathing (C: 31 ± 5.1, ADO: 30 ± 4.5 min/h) when the lesions encompassed Pf or the sector immediately rostral to Pf that retained the capacity to regulate hypoxic inhibition. Smaller lesions created by the insertion of needles also eliminated the depressant effects of ADO when disruptions were within Pf or a rostral component of the thalamic cortical activating system. It is concluded that 1) a medial thalamic sector is critically involved in ADO-induced apnea and 2) ADO-dependent and ADO-independent mechanisms mediate hypoxic inhibition.

Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations

1994 ◽  
Vol 77 (6) ◽  
pp. 2734-2739 ◽  
Author(s):  
B. J. Koos ◽  
B. A. Mason ◽  
O. Punla ◽  
A. M. Adinolfi
Keyword(s):  
Brain Stem ◽  
Fetal Brain ◽  
Normal Incidence ◽  
Halothane Anesthesia ◽  
Microdialysis Probe ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Arterial Po2

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.

Adenosine stimulates breathing in fetal sheep with brain stem section

1992 ◽  
Vol 72 (1) ◽  
pp. 94-99 ◽  
Author(s):  
B. J. Koos ◽  
A. Chao ◽  
W. Doany
Keyword(s):  
Brain Stem ◽  
Blood Gases ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Arterial Infusion ◽  
Fetal Sheep ◽  
Stem Section ◽  
Peripheral Arterial ◽  
Arterial Po2 ◽  
The Brain ◽  
Pontomedullary Junction

Breathing responses to adenosine were determined in 12 chronically catheterized fetal sheep (greater than 0.8 term) in which hypoxic inhibition of breathing had been eliminated by brain stem section. The caudal extent of transection varied from the rostral midbrain to the pontomedullary junction. Isocapnic hypoxia [delta arterial PO2 (PaO2) of -12 Torr] doubled the incidence and depth of breathing activity and increased the incidence of eye movements. Intra-arterial infusion of adenosine (0.30 +/- 0.03 mg.min-1.kg fetal wt-1) increased the incidence and amplitude of breathing without affecting blood gases. Adenosine did not significantly alter the incidence of eye activity. Intra-arterial injection of oligomycin (120 +/- 26 micrograms/kg fetal wt), an inhibitor of mitochondrial oxidative phosphorylation, also stimulated breathing activity. In four fetuses with brain stem section, peripheral arterial chemodenervation blunted the stimulatory effects of hypoxia on breathing activity and abolished altogether the excitatory effects of adenosine. It is concluded that 1) hypoxia and adenosine likely inhibit breathing in normal fetuses by affecting similar areas of the brain stem and 2) in fetuses with brain section, hypoxic hyperpnea depends on peripheral and central mechanisms, whereas adenosine stimulates breathing via the peripheral arterial chemoreceptors.

Effect of Ethanol on 15-Hydroxyprostaglandin Dehydrogenase Activity in the Brain Stem of the Near-Term Fetal Sheep

1991 ◽  
Vol 16 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Deirdre Treissman ◽  
Graeme N. Smith ◽  
John Patrick ◽  
James F. Brien
Keyword(s):  
Brain Stem ◽  
Dehydrogenase Activity ◽  
Fetal Sheep ◽  
Near Term ◽  
The Brain

Respiratory Effects of H+ and Dinitrophenol Injections into the Brain Stem Subarachnoid Space of Fetal Lambs

1975 ◽  
Vol 53 (5) ◽  
pp. 726-733 ◽  
Author(s):  
A. H. Jansen ◽  
B. J. Russell ◽  
V. Chernick
Keyword(s):  
Brain Stem ◽  
Subarachnoid Space ◽  
Extracellular Fluid ◽  
Ventral Surface ◽  
Metabolic Inhibitors ◽  
Blood Gas ◽  
Respiratory Response ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
The Brain

Mock cerebrospinal fluid (pH 5.37–8.38) or 2,4-dinitrophenol (DNP) (0.15–1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

1990 ◽  
Vol 69 (1) ◽  
pp. 136-140 ◽  
Author(s):  
B. J. Koos ◽  
K. Matsuda ◽  
G. G. Power
Keyword(s):  
Fetal Heart ◽  
Fetal Brain ◽  
Cardiovascular Responses ◽  
Dependent Manner ◽  
Brain Oxygenation ◽  
Fetal Sheep ◽  
Fetal Breathing ◽  
Dose Dependent ◽  
Arterial Po2 ◽  
The Brain

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

Surgical Approaches to the Brain Stem

1993 ◽  
Vol 4 (3) ◽  
pp. 457-468 ◽  
Author(s):  
Dennis Y. Wen ◽  
Roberto C. Heros
Keyword(s):  
Brain Stem ◽  
Surgical Approaches ◽  
The Brain

ADRENERGIC INPUTS TO THE AMYGDALA AND THE CONTROL OF GONADOTROPHIN RELEASE

1979 ◽  
Vol 90 (3) ◽  
pp. 385-393 ◽  
Author(s):  
José Borrell ◽  
Flavio Piva ◽  
Luciano Martini
Keyword(s):  
Brain Stem ◽  
Dopamine Receptor ◽  
Serum Levels ◽  
Female Rats ◽  
Receptor Blocker ◽  
Dopaminergic Drug ◽  
Gonadotrophin Secretion ◽  
Biphasic Effect ◽  
Adrenergic Blocker ◽  
The Brain

ABSTRACT Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.

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