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Biomedical subjects

A Gjedde

Publications and source records attributed to A Gjedde.

At least 145 records · Page 8Linked to original sources
PubMed1992

Lateralization of phonetic and pitch discrimination in speech processing.

Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception.

Acoustic Stimulation↗
PubMed1992

3-O-methyldopa administration does not alter fluorodopa transport into the brain.

To determine if 3-O-methyldopa (3OMD) significantly inhibits the transport of 6-[18F]fluorodopa (6-FD) into the brain at the concentration normally encountered during L-dopa administration, we performed 6-FD studies with positron emission tomography in cynomolgus monkeys in the presence and absence of 3OMD. Infusion of 3OMD was designed to produce plasma concentrations equivalent to those seen in patients on chronic L-dopa therapy. Plasma 3OMD levels of 39 +/- 4 microM did not alter the blood-brain transfer rate of 6-FD. 6-FD positron emission tomographic studies in parkinsonian patients will therefore not be altered by 3OMD present in the blood in those patients taking L-dopa preparations. These results do not support the hypothesis that transport of L-dopa into the brain is inhibited by 3OMD to cause the declining response seen in patients with advanced Parkinson's disease.

Amino Acid Transport Systems↗
PubMed1992

Density of perfused capillaries in living human brain during functional activation.

Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.

Brain↗
PubMed1992

Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen.

We measured the rate of washout of 15O-labeled water generated from labeled oxygen accumulated in brain after bolus [15O]O2 inhalation, and compared the washout with that of labeled water measured with H215O. Contrary to the original expectation, the radioactive water generated from labeled oxygen failed to leave the brain tissue at the rate predicted by exogenous water. Therefore, the use of a separately measured value for exogenous water clearance led to an error in the calculation of oxygen consumption. A new method presented in this paper eliminated the error by yielding oxygen consumption in a single oxygen study. We used time-weighted integration to estimate three parameters, including the unidirectional clearance from blood to brain (KO2(1)), the fractional clearance of the distribution volume in brain (kO2(2)), and the vascular volume correction (VO). We showed that the clearance of oxygen from blood to brain can be estimated with acceptable precision by this new approach, and that the new method yields a reliable measure of oxygen consumption.

Administration, Inhalation↗
PubMed1992

Effects of vasopressin on blood-brain transfer of methionine in dogs.

We used a simplified probe detection system for positron-emitting radionuclides in order to measure blood-brain barrier transport of amino acids in anesthetized dogs. Plasma and brain time-activity curves were recorded after intravenous bolus injection of L-[11C]methionine before and after administration of 1 microgram of vasopressin. Three-compartment models with three or four transfer coefficients were used to derive the kinetics of L-[11C]methionine uptake in brain. The blood-brain clearance of the tracer (K1) was 0.075 ml ml-1 min-1 before and 0.041 ml ml-1 min-1 after injection of vasopressin. The partition volume and the initial distribution (plasma) volume of methionine were unchanged and within the expected limits. The net accumulation rate of methionine (K), estimated by both the four-parameter (kinetic) and three-parameter (graphic) approaches, decreased after vasopressin injection in all six studies.

Animals↗
PubMed1992

In vivo distribution of CGS-19755 within brain in a model of focal cerebral ischemia.

The blood-brain barrier permeability of the competitive N-methyl-D-aspartate receptor antagonist CGS-19755 [cis-4-(phosphonomethyl)-2-piperidine carboxylic acid] was assessed in normal and ischemic rat brain. The brain uptake index of CGS-19755 relative to iodoantipyrine was assessed using the Oldendorf technique in normal brain. The average brain uptake index in brain regions supplied by the middle cerebral artery was 0.15 +/- 0.35% (mean +/- SEM). The unidirectional clearance of CGS-19755 from plasma across the blood-brain barrier was determined from measurements of the volume of distribution of CGS-19755 in brain. These studies were performed in normal rats and in rats with focal cerebral ischemia produced by combined occlusion of the proximal middle cerebral artery and ipsilateral common carotid artery. In normal rats the regional plasma clearance across the blood-brain barrier was low, averaging 0.015 ml 100 g-1 min-1. In ischemic rats this clearance value averaged 0.019 ml 100 g-1 min-1 in the ischemic hemisphere and 0.009 ml 100 g-1 min-1 in the nonischemic hemisphere. No significant regional differences in plasma clearance of CGS-19755 were observed in either normal or ischemic rats except in cortex injured by electrocautery where a 14-fold increase in clearance across the blood-brain barrier was measured. We conclude that CGS-19755 crosses the blood-brain barrier very slowly, even in acutely ischemic tissue.

Animals↗
PubMed1991

Atrial natriuretic peptide augments the blood-brain transfer of water but not leucine and glucose.

Recent evidence predicts an effect of atrial natriuretic peptide (ANP) on the blood-brain transfer of water. To test this prediction, we measured the blood-brain transfer of water, L-leucine, and D-glucose in 9 brain regions of male rats after intravenous injection of 10 pmol ANP. The peptide elicited an increase of the permeability-surface area (PaS) product of labeled water by 28-108% while the PaS products of leucine and glucose remained unchanged. Cerebral blood flow increased 15-48% while cardiac output and plasma volume in brain did not alter, indicating no change of capillary surface area (CSA). Regionally, the CSA varied from 63 cm2/g (striatum) to 97 cm2/g (colliculi) and the fraction of capillaries contributing to the total vascular volume varied from 29% (olfactory bulb/lobe) to 62% (striatum). The blood-brain barrier (BBB) permeability to water (5.7 micron/s) was an order of magnitude higher than to glucose (0.4 micron/s) or to leucine (0.3 micron/s).

Animals↗
PubMed1991

Dopa decarboxylase activity of the living human brain.

Monoaminergic neurons use dopa decarboxylase (DDC; aromatic-L-amino-acid carboxy-lyase, EC 4.1.1.28) to form dopamine from L-3,4-dihydroxyphenylalanine (L-dopa). We measured regional dopa decarboxylase activity in brains of six healthy volunteers with 6-[18F]fluoro-L-dopa and positron emission tomography. We calculated the enzyme activity, relative to its Km, with a kinetic model that yielded the relative rate of conversion of 6-[18F]fluoro-L-dopa to [18F]fluorodopamine. Regional values of relative dopa decarboxylase activity ranged from nil in occipital cortex to 1.9 h-1 in caudate nucleus and putamen, in agreement with values obtained in vitro.

Brain↗
PubMed1991

Bi-affinity alpha 1-adrenoceptor binding in normal rat brain in vivo.

The specific binding in rat brain in vivo of [125I]HEAT ([125I]iodo-2-[beta-(4-hydroxyphenyl)ethylamino methyl), a selective alpha 1-adrenoceptor ligand, was analyzed by a method designed to distinguish sites with different affinities. The data indicate at least two sites with different affinities for the alpha 1-adrenoreceptor in normal rat brain in vivo: a high-affinity site with Kd (half-saturation constant) of 3.6 +/- 0.7 nM (AV +/- SD), and a low-affinity site with Kd of 668 +/- 552 nM. The density (Bmax) of the high-affinity site in nine brain regions--auditory, visual, sensorimotor (four layers) and frontal cortex and lateral thalamic and medial geniculate nuclei--varied from 2.2 +/- 0.8 to 14.6 +/- 0.6 pmole/g, while the low-affinity range was 149 +/- 44 to 577 +/- 30 pmole/g. The results also revealed a very dynamic relationship between the two sites regulated by the concentration of the ligand ranging from 80% preponderance of the high-affinity sites at low ligand concentrations to more than 95% preponderance of the low-affinity sites at high ligand concentrations.

Animals↗
PubMed1991

Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization.

The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using [U-11C]-D-glucose as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62 +/- 19 (mean +/- SEM) mumol hg-1 min-1, and the half-saturation constant was found to be 4.1 +/- 2.3 mM.

Biological Transport↗
PubMed1991

Pathophysiology of the human brain after stroke, monitored by positron emission tomography.

Six stroke patients had positron tomograms both in the acute stage of the cerebrovascular accident (16 to 38 h after onset), and one week later. In and around the infarct, the studies revealed a wide range of metabolic states. In the healthy regions of the brain, all measured physiological variables, including the density of capillaries that transported glucose, blood flow, and oxygen and glucose metabolism, changed in parallel (recruitment). In the regions suffering the consequences of stroke, in the second study, the physiological couple between capillary density, metabolism, and flow was significantly impaired, and the impairment was proportional to the severity of ischemia in the first study. The research report of these findings appeared in the Journal of Cerebral Blood Flow and Metabolism (Gjedde et al. 1990).

Aged↗
PubMed1991

In vivo binding of nimodipine in the brain: II. Binding kinetics in focal cerebral ischemia.

We report the binding characteristics of [3H]nimodipine to normal and ischemic brain in vivo. We used the 1,4-dihydropyridine, nimodipine, to label the L-type voltage-sensitive calcium channel in focal cerebral ischemia after occlusion of both the middle cerebral and ipsilateral common carotid arteries in rats. Varying concentrations of [3H]nimodipine were infused 3.5 h after the onset of ischemia and circulated for 30 min before the brain was obtained for autoradiography and determination of regional nimodipine content. In separate sets of experiments, the metabolites of nimodipine were determined and the conditions for equilibrium of nimodipine distribution were established. Increased nimodipine uptake was observed in ischemic regions. This increased binding was saturable and specific with an affinity constant, KD, of 0.45 nM and a maximal regional binding capacity, Bmax, ranging from 3.1 to 10.9 pmol/g. Only binding to ischemic tissue was specific and saturable whereas that in nonischemic tissue was nonspecific. In vivo binding of nimodipine may be used to identify cell membrane depolarization and calcium channel activation in focal cerebral ischemia.

Animals↗
PubMed1991

Activity of the dihydropyridine calcium channels following cerebral ischemia.

With an in-vivo autoradiographic method the binding of 3H-nimodipine (CAS 66085-59-4) and cerebral blood flow (14C-iodoantipyrine method) were measured in rat brain after occlusion of the middle cerebral and common carotid arteries. The dependence of the binding to neuronal cellular membranes on the duration of ischemia can be interpreted as indicator of the tissue's functional state or its responsiveness to therapy with calcium entry blockers. In the two analyzed structures, dorsolateral caudate and overlying sensorimotor cortex, the appearance of infarction is preceded by an activation of the nimodipine binding sites followed by persistent decline of the binding intensity. Binding to nimodipine may therefore be a useful marker of ischemic but salvageable brain tissue.

Animals↗
PubMed1991

Validation of simultaneous PET emission and transmission scans.

A technique for performing simultaneous PET emission and transmission scans is validated in a fluoro-deoxyglucose study. A point source masked into a fan beam of annihilation photons orbits the patient section under study. Coincident events are sorted into two buffers, or rejected, based on the source's position. Both static and dynamic frames of independent and simultaneous studies are compared. The noise effective count rate is reduced to 62% of the value during normal studies. However, the increase in the coefficient of variation in cortical regions is less than 6%. The RMS difference between profile contours through many brain regions is approximately 40% higher comparing two simultaneous emission/transmission scans than when the same analysis is performed on independent emission scans. This difference appears to be due to the noise patterns arising from the use of different transmission scans.

Adult↗
PubMed1991

Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose.

Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +/- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +/- 2 mumol hg-1 min-1.

Animals↗
PubMed1991

Measurements of glucose phosphorylation with FDG and PET are not reduced by dephosphorylation of FDG-6-phosphate.

To improve the measurements of glucose metabolism in the human brain, we imposed biologic constraints on the deoxyglucose model with and without dephosphorylation of FDG-6-phosphate (the k4*- and k3*-models). The constraints included constant transport and phosphorylation ratios (tau and phi) and a common partition volume (K1/k2) for tracer [18F]FDG and glucose. In the presence of significant dephosphorylation, the k3*-model yielded time-dependent estimates of the phosphorylation coefficient (k3*), while the K4*-model yielded time-independent estimates. However, the two models yielded practically identical measurements of regional cerebral glucose metabolism in PET studies of six normal volunteers when the phosphorylation affinity ratio (the k3*/k3 ratio of FDG and glucose) and tracer circulation time were 0.30 and 20 min for the k3*-model and 0.33 and 45 min for the k4*-model.

Brain↗
PubMed1990

Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels.

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.

Animals↗