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Biomedical subjects

A Gjedde

Publications and source records attributed to A Gjedde.

At least 109 records · Page 6Linked to original sources
PubMed1996

Local cerebral glucose utilization in fetal guinea pigs at 0.75 gestation.

OBJECTIVE: Using the 2-deoxyglucose method, measurements of local cerebral glucose utilization in large fetal animals are very difficult and expensive. To circumvent these problems we recently modified the 2-deoxyglucose method for use in the fetal guinea pig in utero (Berger et al., J Neurochem 1994; 63: 271-279). The present study was designed to measure the rates of local cerebral glucose utilization in fetal guinea pigs at 0.75 of gestation. STUDY DESIGN: After intravenous injection of 14C 2-deoxyglucose into the dams, local cerebral glucose utilization of the fetuses was measured from the time integral of the tracer in the maternal plasma and the autoradiographically determined concentration of the tracer in various parts of the fetal brain. RESULTS: Fetal cerebral glucose utilization was low as compared to adult animals and varied in different brain structures from 19 +/- 4 to 29 +/- 7 mumol/100 g/min. CONCLUSION: This study demonstrates the feasibility to measure local cerebral glucose utilization in undisturbed fetal guinea pigs in utero. We conclude that the low rate of cerebral glucose utilization and its small overall variability may reflect the neurological immaturity of the fetal brain.

Animals↗
PubMed1996

Cerebral [15O]water clearance in humans determined by PET: I. Theory and normal values.

When used to measure blood flow in the brain, water leaves a residue in the vascular bed that influences the estimation of blood flow by current methods. To assess the magnitude of this influence, we developed a two-compartment model of blood flow with separate parameters for transport and vascular distribution of brain water. Maps of the water clearance, K1 into brain tissue, separated from the circulation by a measurably resistant blood-brain barrier (BBB), were generated by time-weighted integration. Depending on the validity of the assumptions underlying the two-compartment model presented here, the maps revealed a significant overestimation of the clearance of water when the vascular residue was ignored. Maps of Vo, the estimate of the apparent vascular distribution volume of tracer H2(15)O, clearly revealed major cerebral arteries. Thus, we claim that the accumulation of radioactive water in brain tissue also reflects the volume of the arterial vascular bed of the brain.

Body Water↗
PubMed1995

Metabolism and blood-brain clearance of L-3,4-dihydroxy-[3H]phenylalanine ([3H]DOPA) and 6-[18F]fluoro-L-DOPA in the rat.

6-[18F]fluoro-L-DOPA (FDOPA) has been used as a tracer for the cerebral activity of L-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL.hg-1.min-1) in six brain regions was 60% higher than that of [3H]DOPA.

Animals↗
PubMed1995

Serotonin 5-HT2 receptor availability in chronic cocaine abusers.

Serotonin 5-HT2 receptor availability was evaluated in chronic cocaine abusers (n = 19) using positron emission tomography and F-18 N-methylspiperone and was compared to control subjects (n =19). 5-HT2 Receptor availability was measured in frontal, occipital, cingulate and orbitofrontal cortices using the ratio of the distribution volume in the region of interest to that in the cerebellum which is a function of Bmax/Kd. 5-HT2 Receptor availability was significantly higher in cingulate and orbitofrontal cortices than in other frontal regions or occipital cortex. The values were not different in normal subjects and cocaine abusers. These results did not show any changes in 5-HT2 receptor availability in cocaine abusers as compared to the control subjects.

Adolescent↗
PubMed1995

Effect of injury on the bi-affinity alpha 1-adrenoreceptor binding in rat brain in vivo.

Focal freezing lesions in rats cause a widespread decrease of cortical glucose utilization in the lesioned hemisphere, probably as a reflection of depressed cortical activity. The noradrenergic neurotransmitter system was implicated in these alterations when it was demonstrated that prazosin, a specific norepinephrine (NE) antagonist at alpha 1-adrenergic receptors, prevented their development. In normal rat brain, specific binding of [125I]HEAT [(+/-)2-(3-[125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone], another selective alpha 1-adrenoreceptor ligand, was demonstrated in vivo at sites consistent with the alpha 1A- and alpha 1B-adrenoreceptor subtypes. In the present study, the effect of a freezing lesion on specific binding of [125I]HEAT in rat brain in vivo was determined three days after traumatization when cortical glucose use suggested the greatest degree of functional depression. The steady-state volumes of distribution of [125I]HEAT three days after injury were significantly increased in all the cortical areas of the lesioned hemisphere, but not in the subcortical structures. Injury did not modify the binding affinities for HEAT. However, a statistically significant increase in the number of low-affinity binding sites for this ligand was demonstrated in all cortical areas of the lesioned hemisphere, but not in subcortical structures. The traumatization did not modify Bmax estimates for the high-affinity binding of HEAT. The results support the hypothesis that changes in the noradrenergic system are of functional importance in brain injury and that at least some effects of injury are mediated by alpha 1B-adrenergic receptors.

Animals↗
PubMed1995

Regulation of DOPA decarboxylase activity in brain of living rat.

To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3H]DOPA. The unidirectional blood-brain clearance of [3H]DOPA (K1D) was 0.049 ml g-1 min-1. The relative DDC activity (k3D) was 0.26 min-1 in striatum, 0.04 min-1 in hypothalamus, and 0.02 min-1 in hippocampus. In striatum, 3,4-[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate constant of 0.013 min-1, [3H]homovanillic acid ([3H]HVA) was formed from [3H]DOPAC at a rate constant of 0.020 min-1, and [3H]HVA was eliminated from brain at a rate constant of 0.037 min-1. Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k3D was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers.

OBJECTIVE: The authors tested the prediction of temporal cortex activation during experimentally induced anxiety by using positron emission tomography and the [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF) changes in normal volunteers challenged with a bolus injection of cholecystokinin tetrapeptide (CCK4). METHOD: Eight right-handed healthy subjects (five male, three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans separated by 15-minute intervals; each scan followed an intravenous bolus injection of either saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once, as the first or second bolus, in a random-order, placebo-controlled, double-blind fashion. Two of the three placebo conditions were nominally identical, and the remaining placebo was used to control for anticipatory anxiety. Magnetic resonance imaging scans were obtained for subsequent anatomical correlation of blood flow changes. RESULTS: CCK4, but not placebo, elicited a marked anxiogenic response, reflected by robust increases in subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated with 1) robust and bilateral increases in extracerebral blood flow in the vicinity of the superficial temporal artery territory and 2) CBF increases in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and the cerebellar vermis. CONCLUSIONS: Some of the temporopolar cortex CBF activation peaks previously reported in humans in association with drug- and non-drug-induced anxiety, as well as the increase in regional CBF in the claustrum-insular-amygdala region, may be of vascular and/or muscular origin.

Adult↗
PubMed1995

Regional striatal DOPA transport and decarboxylase activity in Parkinson's disease.

METHODS: We measured blood-brain barrier transport and decarboxylation of 6-[18F]fluoro-L-DOPA (FDOPA) using PET in patients with Parkinson's disease (n = 7, 57 +/- 7 yr) and age-matched control subjects (n = 7, 60 +/- 6 yr). To visually present regional changes of FDOPA uptake in Parkinson's disease, we introduced maps of FDOPA uptake relative to occipital cortex, averaged across control subjects and Parkinson's disease patients in an MRI-based stereotaxic coordinate space. RESULTS: There was no significant changes in the blood-to-brain transport of FDOPA (KD1) in Parkinson's disease. The KD1 values of the head of caudate were lower than those of putamen in both normal subjects and Parkinson's disease patients. In Parkinson's disease, the activity of L-DOPA decarboxylase (DDC) was differentially reduced in subdivisions of striatum. The residual DDC activity was 63% of the control value in the head of caudate nucleus, 54% in the anterior putamen and 39% in the posterior putamen. The DDC activity in frontal and occipital cortices remained unchanged by the disease. Subtraction of averaged FDOPA uptake maps (control minus Parkinson's disease) visualized a spatial pattern of pathological changes in FDOPA uptake common to Parkinson's disease patients. CONCLUSION: The striatal blood-to-brain transport of FDOPA remained unchanged while the DDC activity was differentially reduced within the striatum in Parkinson's disease. We found the FDOPA uptake maps useful in identifying altered patterns of FDOPA metabolism common in Parkinson's disease.

Biological Transport↗
PubMed1994

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗
PubMed1994

Distribution of histamine H3 binding in forebrain of mouse and guinea pig.

To map the unknown distribution of histamine H3 binding sites, we compared autoradiographs of the binding of the H3 agonist N alpha-[3H]methylhistamine ([3H]NAMH) in the forebrain of mouse and guinea pig. Saturation binding revealed the presence of a single site with apparent affinity of 0.75 nM in the mouse and 1.2 nM in the guinea pig. Binding constants were nearly identical in male and female mice. The rank order of [3H]NAMH binding in mouse brain was striatum > insular cortex > neocortex, as previously observed in the rat. In the guinea pig, the rank order was insular cortex > striatum approximately neocortex. The Bmax of [3H]NAMH in insular cortex of both species was close to 60 fmol/mg. Thus, the guinea pig differs from the rodent in that the highest density of H3 binding was present in cortical rather than subcortical structures.

Animals↗
PubMed1994

Histamine H3 binding sites in rat brain: localization in the nucleus of the solitary tract.

The distribution of high-affinity binding sites for the histamine H3 agonist [3H]-N alpha-methylhistamine ([3H]NAMH, 4 nM) in the rat brain was examined by autoradiography. Binding in all brain regions was displaceable with the H3 antagonist thioperamide (2 microM). The pattern of H3 binding was heterogeneous: highest levels were in the striatum and substantia nigra, which receives sparse histaminergic innervations. Intermediate H3 binding was present in neocortex and diencephalon, while low binding was evident in the medial septum and dorsal hippocampus. Hitherto unreported H3 binding sites were noted in the dorsolateral tegmentum and in the nucleus of the solitary tract (NTS). Because the NTS receives a dense histaminergic innervation, [3H]NAMH binding in the NTS was further studied by Scatchard analysis. The presence of saturable binding (Bmax = 10 +/- 4 fmol/mg, Kd = 0.6 +/- 0.3 nM, n = 3) suggested that histamine may act via H3 receptors in the NTS.

Animals↗
PubMed1994

Subclasses of histamine H3 antagonist binding sites in rat brain.

Histamine H3 antagonists have been reported to discriminate subclasses of histamine H3 agonist binding in rat cortical membranes. This phenomenon was investigated by autoradiography of cryostat sections of rat forebrain labelled with [3H]N alpha-methylhistamine ([3H]NAMH, 4 nM). Displacement curves with thioperamide detected a single site in cortex and striatum (pIC50 = 8.18 +/- 0.03). However, Hill coefficients (nH = 0.51 +/- 0.12) suggested the possible presence of multiple binding sites. Displacement with burimamide was consistent with two site models in all brain regions examined (pIC50(A) = 7.9 +/- 1.5; pIC50(B) = 5.6 +/- 0.7), except for the medial septum where a single site was detected. Elsewhere, the relative abundance of the two sites displaced by burimamide (H3A:H3B) appeared to be 1:2. Thioperamide may have failed to discriminate two sites because the IC50s were too similar to be distinguished in the present autoradiographic study.

Animals↗
PubMed1994

Brain uptake of alpha-[14C]methyl-para-tyrosine in the rat.

The blood-brain permeabilities of L-[3H]tyrosine and the tyrosine hydroxylase (TH) inhibitor alpha-[14C]methyl-para-tyrosine ([14C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K1) for L-[3H]tyrosine (6.2 ml hg-1 min-1) was significantly greater than the rates for L-[14C]AMPT (2.8 ml hg-1 min-1) and D-[14C]AMPT (0.8 ml hg-1 min-1). The apparent volume of distribution (Vf) for L-[14C]AMPT in striatum (72.5 +/- 4.0 ml hg-1) did not differ from the Vf in other brain regions. The homogeneous distribution of L-[14C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography.

Animals↗