SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The author hypothesizes that individuals who suffer brain hypoxia prenatally, perinatally, or immediately postnatally constitute a population at risk for minimal brain dysfunction and for schizophrenia in adulthood. This hypothesis has implications for early intervention with children who have MBD and their families and for multidisciplinary management of these cases throughout childhood.
Brain extracellular potassium [( K+]ec) in the ventral respiratory group of the medulla and the phrenic neurogram were recorded in anesthetized vagotomized peripherally chemodenervated ventilated cats during progressive isocapnic carbon monoxide (CO) hypoxia. During hypoxia, the phrenic neurogram was progressively depressed and became silent when arterial O2 content (CaO2) was reduced by 62 +/- 3% (SE). Gasping was seen in the phrenic neurogram when CaO2 was reduced by 78 +/- 1%. Medullary [K+]ec, an indicator of energy production failure due to O2 insufficiency, was 3.2 +/- 0.4 mM before hypoxia and was statistically unchanged at the onset of phrenic apnea during CO hypoxia (4 +/- 0.7 mM). By the onset of gasping, [K+]ec had increased to 6.1 +/- 1 mM, a value that tended to be different from control (P less than 0.1). After initiation of gasping, the rate of rise of [K+]ec increased, and [K+]ec reached a maximum value of 14.3 +/- 2.7 mM before hypoxia was terminated. With reoxygenation, [K+]ec returned to control levels within 20 min. On the basis of these results, we have drawn two major conclusions. 1) Hypoxic depression to the point of phrenic apnea does not appear to be caused by medullary energy insufficiency as measured by loss of [K+]ec homeostasis. 2) The rapid rise in [K+]ec in the medulla that characterizes severe hypoxia is closely associated with the onset of gasping in the phrenic neurogram, suggesting that gasping may serve as a marker for loss of medullary ionic homeostasis and thus onset of medullary energy insufficiency during hypoxia.
The effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in brain hypoxia have been studied in mice using the following experimental models: hypobaric hypoxia induced by low atmospheric pressure, histotoxic hypoxia induced by 12.5 mg/kg KCN i.p., and complete ischemia induced by decapitation. ET-1 and ET-3 were injected intracerebroventricularly (i.c.v.) 15 min before the tests. Forebrain tissue concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured 15 min following i.c.v. administration of ET-1 (5 pmol/mouse) and ET-3 (10 pmol/mouse). ET-1 (1-5 pmol/mouse) and ET-3 (5-25 pmol/mouse) showed a dose-dependent increase in the survival/gasping time in all models of hypoxia. The effect reached its maximum between 15 and 30 min after ET administration and lasted for about 120 min. ET-1 and ET-3 did not significantly change the brain levels of 6-keto-PGF1 alpha and TxB2. The protective effect of ET-1 and ET-3 was unexpected, because endothelins (ETs) are the most potent vasoconstrictors known, and in doses close to those used in this study they cause vasoconstriction and decrease in cerebral blood flow. The protection was not likely to be due either to stimulation of the endogenous release of prostacyclin (PGI2) or to a decrease in the deleterious prostanoid thromboxane A2 (TxA2). Additional experiments are necessary to explain the cerebroprotective effects of ET-1 and ET-3.
The effects of acute brain hypoxia on pulmonary hemodynamics were investigated in anesthetized dogs with the vagus and carotid sinus nerves intact and cut. Following ligation of collateral vessels, brain hypoxia was induced by pumping arterial blood through a ventilated extracorporeal lung to the external carotid arteries for 5 min. In the intact-nerve group brain hypoxia caused no change in pulmonary and systemic vascular pressures and resistances. In the cut-nerve group brain hypoxia caused an increase in mean pulmonary artery, left atrial, pulmonary artery pulse, and mean aortic pressures. Cardiac output, dP/dt, central blood volume, and total peripheral resistance increased but pulmonary vascular resistance and lung extravascular thermal volume were unchanged. It is concluded that acute brain hypoxia does not increase pulmonary vascular resistance but may increase pulmonary blood volume resulting from increased left ventricular afterload.
Explore the source record for details and available documents.
The effects of graded brain hypoxia on respiratory cycle timing, the lung inflation reflex, and respiratory compensation for an inspiratory flow-resistive load were studied in unanesthetized goats. Two models, inhalation and CO and acute reduction of brain blood flow (BBF) were used to produce comparable levels of brain hypoxia. The lung inflation reflex was assessed as the ratio of inspiratory time of an occluded breath to that of the preceding spontaneous breath (TIoccl/TIspont). Compensation for flow-resistive loading was assessed as the effect of the load upon the airway occlusion pressure response to rebreathing CO2 (delta P 0.1/delta PCO2). Major findings were 1) severe brain hypoxia (HbCO of 60% or BBF of 42%) caused tachypnea due to a 50% or more reduction of expiratory time but only a 20% or less reduction of inspiratory time; 2) moderate carboxyhemoglobinemia (HbCO of 25-30%) enhanced TIoccl/TIspont from 1.5 +/- 0.1 at control to 2.1 +/- 0.1, while severe brain hypoxia (HbCO of 60% and BBF of 42%) reduced the ratio to 1.0 +/- 0.2; and 3) compensation for a flow-resistive load, manifested by increases of delta P 0.1/delta PCO2 of 75-300% in the control state, was abolished at HbCO of 45-50% and BBF of 60%. The data suggest that in unanesthetized animals brain hypoxia elicits tachypnea largely by an effect on the expiratory phase of the bulbopontine timing mechanism. The observed enhancement of the lung inflation reflex and abolition of flow-resistive load compensation are best explained by hypoxic depression of higher than brain stem neural function.
The paper describes differences of hypoxic and circulatory hypoxias (i.e. brain ischemia) which cause decreases not only in the supply of O2, but in the delivery of glucose and other oxidation substrates and in venous return, which is attended by the accumulation of metabolic products in the brain tissue. It also considers the mechanisms of primary and secondary brain ischemia occurring with decreased cerebral circulation due to breakdown of cerebral blood flow autoregulation at its lower and upper borders to develop cytotoxic or vasogeneous brain tissue edema with possible compression of the microcirculatory bed in the latter case. Emphasis is laid on the significance of autoimmune reactions occurring with the impaired blood-brain barrier due to different types of cerebral circulatory disorders, which gives an insight into the cause of progressive damage to the brain in some cases despite its single damage. The paper outlines current therapies for brain ischemia, including those that exert effects on metabolic disturbances and neurosurgical reparative operations. In conclusion, the paper considers a new nontraditional way of increasing collateral CBF by decreasing blood flow pseudoturbulence with special high molecular-weight linear polymer solutions by the Thoms-effect method (1948). The prospects for using this approach in patients with brain ischemia are substantiated by a number of the established facts: 1) the above patients have higher hemodynamic blood flow resistance which may be corrected by adding a polymer solution into the sample in in vitro tests; 2) there was an inverse relationship of the intrinsic plasma concentrations of high molecular-weight fragments of DNA and hemodynamic resistance to the changes in plasma DNA properties in stroke patients.
Two series of experiments were performed. In the first one experiments were carried out in Koletsky genetically hypertensive lean female rats and in the normotensive female rats of Wistar strain. Glucose intolerance was induced by oligemic brain hypoxia (4 hours of occlusion of both common carotid arteries followed by 44 hours reperfusion). Brain water content were used as a marker of brain edema. Changes in insulinemia and specific insulin binding were used as expression of regulative mechanisms participating in modification of glucose tolerance. The effect of terguride (trans-dihydro-lisuride) was tested. Brain hypoxia induced glucose intolerance in both strains of rat but brain edema was found only in the normotensive females. Both abnormalities were alleviated by terguride treatment. Basal glycaemia was not changed either by the brain hypoxia or by terguride treatment, except normotensive female where brain hypoxia induced hyperglycaemia. The second series of experiments were carried out in the normotensive females. The arrangement of experiments was the same as in first series except omission of the final glucose tolerance test. Brain hypoxia causes increase in brain water content. The mentioned elevation of brain water content was alleviated by terguride treatment. Insulin binding to erythrocytes was not influenced by brain hypoxia. Terguride treatment shows decrease of insulin binding to erythrocytes. Brain hypoxia elevates insulinemia which was not alleviated by terguride treatment.
Although the dominant respiratory response to hypoxia is stimulation of breathing via the peripheral chemoreflex, brain hypoxia may inhibit respiration. We studied the effects of two levels of brain hypoxia without carotid body stimulation, produced by inhalation of CO, on ventilatory (VI) and genioglossal (EMGgg) and diaphragmatic (EMGdi) responses to CO2 rebreathing in awake, unanesthetized goats. Neither delta VI/delta PCO2 nor VI at a PCO2 of 60 Torr was significantly different between the three conditions studied (0%, 25%, and 50% carboxyhemoglobin, HbCO). There were also no significant changes in delta EMGdi/delta PCO2 or EMGdi at a PCO2 of 60 Torr during progressive brain hypoxia. In contrast, delta EMGgg/delta PCO2 and EMGgg at a PCO2 of 60 Torr were significantly increased at 50% HbCO compared with either normoxia or 25% HbCO (P less than 0.05). The PCO2 threshold at which inspiratory EMGgg appeared was also decreased at 50% HbCO (45.6 +/- 2.6 Torr) compared with normoxia (55.0 +/- 1.4 Torr, P less than 0.02) or 25% HbCO (53.4 +/- 1.6 Torr, P less than 0.02). We conclude that moderate brain hypoxia (50% HbCO) in awake, unanesthetized animals results in disproportionate augmentation of EMGgg relative to EMGdi during CO2 rebreathing. This finding is most likely due to hypoxic cortical depression with consequent withdrawal of tonic inhibition of hypoglossal inspiratory activity.
BACKGROUND: The aim of this investigation was to verify whether brain hypoxia represented a risk factor for the occurrence and severity of opioid abstinence syndrome. METHODS: Three newborns who manifested seizure activity as a result of hypoxia, focal brain ischemia, and hypoxia and sepsis, respectively, were compared with 17 neonates who suffered from hypoxia without developing seizure activity. RESULTS: The first three neonates suffered a severe withdrawal syndrome (a rating on the neonatal abstinence score>17), the others did not. CONCLUSIONS: It is hypothesized that brain hypoxia facilitated the occurrence and severity of the withdrawal syndrome because some key neurochemical processes (such as N-methyl-D-aspartate activation, protein kinase C activation and nitric oxide production) are common to both phenomena.
1. We assessed the effects of specific brain hypoxia on the control of inspiratory and expiratory muscle electromyographic (EMG) activities in response to specific carotid body hypoxia in seven awake goats. We used an isolated carotid body perfusion technique that permitted specific, physiological, steady-state stimulation of the carotid bodies or maintenance of normoxia and normocapnia at the carotid bodies while varying the level of systemic, and therefore, brain oxygenation. 2. Isolated brain normocapnic hypoxia of up to 1.5 h duration increased inspired minute ventilation (VI) by means of increases in both tidal volume (VT) and respiratory frequency (fR). Electromyographic activities of both inspiratory and expiratory muscles were augmented as well. These responses were similar to those produced by low levels of whole-body normoxic hypercapnia. We conclude that moderate levels of brain hypoxia (Pa,O2 approximately 40 mmHg) in awake goats caused a net stimulation of ventilatory motor output. 3. Hypoxic stimulation of the carotid bodies alone caused comparable increases in VT and fR, and EMG augmentation of both inspiratory and expiratory muscles whether the brain was hypoxic or normoxic. These responses were quite similar to those obtained over a wide range of whole-body normoxic hypercapnia. We conclude that the integration of carotid body afferent information is not affected by moderate brain hypoxia in awake goats. 4. We found no evidence for an asymmetrical recruitment pattern of inspiratory vs. expiratory muscles in response to carotid body hypoxia or in response to brain hypoxia alone. 5. Our data support the concept that moderate brain hypoxia results in a net stimulation of respiratory motor output. These findings question the significance of 'central hypoxic depression' to the regulation of breathing under physiological levels of hypoxaemia in the awake animal.
This review is a summary of the effects of brain hypoxia on respiration with a particular emphasis on those studies relevant to understanding the cellular basis of these effects. Special attention is given to mechanisms that may be responsible for the respiratory depression that appears to be the primary sequela of brain hypoxia in animal models. Although a variety of potential mechanisms for hypoxic respiratory depression are considered, emphasis is placed on changes in the neuromodulator constituency of the respiratory neuron microenvironment during hypoxia as the primary cause of this phenomenon. Hypoxia is accompanied by a net increase in neuronal inhibition due to both decreased excitatory and increased inhibitory neuromodulator levels. A survey of hypoxia-tolerant cellular systems and organisms suggests that hypoxic respiratory depression may be a manifestation of the depression of cellular metabolism, which appears to be a major adaptation to limited oxygen availability in these systems.
In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.
In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. Previous human studies using 18F-fluoromisonidazole and positron emission tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue hypoxia, which had normalized at repeat scan >48 h later. In the only validation study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia tracer. Here we report a pilot study of 18F-FMISO PET in experimental stroke. Spontaneous hypertensive rats were subjected to distal clip MCAo. Three-hour dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two sessions: 30 mins and 48 h after clip), and 3 with temporary MCAo (45 mins, n=1; 120 mins, n=2; scanning started 30 mins after clip removal). Experiments were terminated by perfusion-fixation for standard histopathology. Late tracer retention was assessed by both compartmental modelling and simple side-to-side ratios. In the initial PET session of the permanent MCAo rat, striking trapping of 18F-FMISO was observed in the affected cortex, which had normalized 48 h later; histopathology revealed pannecrosis. In contrast, there was no demonstrable tracer retention in either temporary MCAo models, and histopathology showed ischemic changes only. These results document elevated 18F-FMISO uptake in the stroke area only in the early phase of MCAo, but not after early reperfusion nor when tissue necrosis has developed. These findings strongly support the validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.
Explore the source record for details and available documents.
This study examines the effect of progressive isocapnic CO hypoxemia on respiratory afterdischarge and the phrenic neurogram response to supramaximal carotid sinus nerve (CSN) stimulation. Twelve anesthetized, vagotomized, peripherally chemodenervated, ventilated cats with blood pressure controlled were studied. During isocapnic hypoxemia, the amplitude of the phrenic neurogram was progressively depressed. In contrast, the increase in peak phrenic amplitude produced by CSN stimulation was unchanged, suggesting that the central respiratory response to CSN stimulation is unaffected by progressive hypoxemia. The time constant of respiratory afterdischarge (tau) was calculated from best-fit plots of phrenic amplitude vs. time after cessation of CSN stimulation. Under control conditions the value of tau was 57.7 +/- 3 (SE) s (n = 12). During progressive isocapnic hypoxemia, tau decreased as a linear function of arterial O2 content (CaO2) such that a 40% reduction of CaO2 resulted in a 48% reduction in tau. This reduction of respiratory afterdischarge may contribute to the genesis of periodic breathing during hypoxia.
Heavily myelinated cultures of newborn mouse cerebellum were exposed to hypoxia and studied by electron microscopy. The cultures were placed in an incubating medium deprived of oxygen (95 to 97 per cent deprivation) for 7 to 60 minutes and fixed immediately for electron microscopy. The amount of oxygen present in the medium and time course of hypoxia were constantly monitored and recorded by an oxygen probe of polarographic oxygen sensor type and a recorder. In contrast to previous in vivo studies, this in vitro model of hypoxic cell injury has provided accurate information concerning the relationship between degree of hypoxia and cell lesion. Hypoxia affected neurons which showed "swelling" and disorganization of cristae in mitochondria and reduced cytoplasmic matrix density due to the dispersion of polysomes. A small population of neurons with an increased cytoplasmic density and "swollen" mitochondria was also noted. Clearing and degeneration of presynaptic terminals and postsynaptic dendrites were observed. After a longer period of hypoxia most neurons showed an extensive degenerative change consisting of rarefaction of cytoplasm and loss of cytoplasmic organelles. In contrast to neuronal changes, no structural alteration was observed in astrocytes and oligodendrocytes.
The main challenge is the investigation of mechanism for apoptosis research and the drug development. Mitochondria have a key position in the production of reactive oxygen species and in the evolution of apoptosis. More possible pathway will be known with the apoptosis investigation. For development of neuroprotective molecules could give strategies the investigation of apoptosis. Exact knowledge of apoptosis provides the possibility to screen new neuroprotective molecules. We developed a research assay, that could provide quantitative and qualitative data about the free radical production and the mitochondrial transmembrane potential using confocal microscopy. Thus, we could screen drug candidate, neuroprotective molecules.