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R Duelli

Publications and source records attributed to R Duelli.

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Decreased glucose transporter densities, rate constants and glucose utilization in visual structures of rat brain during chronic visual deprivation.

The question was investigated whether local changes in glucose transporter densities and transport kinetics can occur when local cerebral glucose utilization (LCGU) is decreased in some brain structures. Unilateral visual deprivation was induced by monocular enucleation in 25 rats. After 1 week, the contralateral structures of the visual system were analyzed for (1) densities of glucose transporters Glut1 and Glut3 (immunoautoradiography), (2) LCGU (2-[14C]deoxyglucose method) and (3) local rate constants (3-O[14C]methylglucose method). The ipsilateral structures served as controls. During chronic visual deprivation Glut1 and Glut3 densities, LCGU and rate constants were significantly decreased in some structures of the visual system and remained unchanged in others. These results indicate a moderate degree of downregulation of glucose transporters, LCGU and rate constants in the visual system during visual deprivation.

Animals

Autoradiographic determination of local cerebral blood flow and local cerebral glucose utilization during chemical stimulation of the nucleus tractus solitarii of anesthetized rats.

This study was conducted to determine whether the decrease in cerebral blood flow (CBF) observed during chemical stimulation of the nucleus tractus solitarius (NTS) can be explained by a decrease in cerebral metabolism. In anesthetized (urethane and chloralose), paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of L-glutamate. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were quantified in 43 brain structures by quantitative autoradiographic techniques using [14C]iodoantipyrine and 2-[14C]deoxyglucose, respectively. During chemical stimulation of the NTS (n = 6), LCBF decreased significantly in 32 of the 43 structures investigated when compared to either a control group with artificial cerebrospinal fluid injection (n = 6), or a controlled hemorrhage group (n = 5). In the controlled hemorrhage group, blood pressure was decreased to a degree comparable to that induced by microinjection of L-glutamate into the NTS. Mean blood flow of all structures investigated was significantly (P < 0.01) lower in the stimulation group than that in the control group and in the hemorrhage group. No significant differences in LCGU were observed between the three investigated groups in all structures examined except for an increase in LCGU in the chemically stimulated NTS site. It is concluded that the decrease in LCBF measured in most brain structures during chemical stimulation of the NTS is not caused by a decrease in LCGU in these structures and may therefore be explained by neurogenic influences on brain vessels.

Animals

Increase of glucose transporter densities (Glut1 and Glut3) during chronic administration of nicotine in rat brain.

Chronic infusion of nicotine is known to result in a distinct pattern of increases in local cerebral glucose utilization (LCGU). The present study addresses the question whether this increase in LCGU is paralleled by (1) a local increase in Glut1 and/or Glut3 glucose transporter densities and (2) a local increase in capillary density in the brain. Nicotine was infused by osmotic minipumps for one week. In cryosections of rat brains local densities of Glut1 (vascular) and Glut3 (neuronal) glucose transporters were measured by immunoautoradiographic methods whereas local capillary densities were determined by an immunofluorescent method. Densities of glucose transporters Glut1 and Glut3 were increased in 12 of the 27 structures investigated. Glut1 was elevated in four additional structures and Glut3 in two more structures. Comparison of the changes in transporter densities with the changes of LCGU measured in a previous study during chronic nicotine infusion showed that LCGU was also elevated in most of these structures. In contrast, capillary density remained unchanged in all structures investigated. It is concluded that one week of nicotine infusion is sufficient to raise the densities of Glut1 and Glut3 glucose transporters predominantly in those structures in which LCGU is elevated. The unchanged capillary density under these conditions indicates an increased density of Glut1 transporters per capillary.

Animals

Parallel changes of blood flow and heterogeneity of capillary plasma perfusion in rat brains during hypocapnia.

Plasma perfusion patterns were investigated in brain capillaries during decreased cerebral blood flow induced by hyperventilation. Anesthetized rats were decapitated 3-4 s after being given an intravenous bolus injection of Evans blue dye. the measured steep increase of the arterial dye concentration at this moment ensures that different capillary plasma transit times are reflected in different intracapillary dye concentrations. The observed heterogeneity of capillary plasma transit time was expressed as the coefficient of variation (means +/- SD) of the intracapillary dye concentrations. For comparison, cerebral blood flow was determined at comparable PCO2 values in a second experimental group. At arterial PCO2 values between 40 and 25 mmHg, the cerebral blood flow and the coefficient of variation of the intracapillary dye concentration decreased with decreasing PCO2, whereas at PCO2 values <25 mmHg cerebral blood flow and coefficient of variation did not correlate with the arterial PCO2. However, it cannot be excluded that the coefficient of variation of the intracapillary dye concentration increases between 25 and 14 mmHg and decreases between 14 and 10 mmHg. It is concluded that the reduction of cerebral blood flow measured during moderate hypocapnia is paralleled by a decreased heterogeneity of the brain capillary perfusion. During severe hypocapnia this relationship is lost, indicating a potential disturbance of the cerebral microcirculation.

Animals

Autoradiographic analysis of the regional distribution of Glut3 glucose transporters in the rat brain.

Glut3 is a glucose transporter protein which facilitates the transport of glucose across the neuronal membranes. The local distribution of Glut3 in the brain is not well known. The present study had the aim to verify the local distribution of Glut3 in the brain and to compare it with the local glucose utilization. A polyclonal antibody directed against the C-terminal peptide sequence of Glut3 was applied to cryosections of rat brains. A secondary antibody was added which had been coupled to 35S. Using autoradiography and radioactive standards, 17 cerebral structures were investigated. The results show moderate differences of Glut3 density in the structures investigated ranging from -23% to +41% of the mean density. The pineal gland was an exception with a density 66% lower than mean. Local cerebral glucose utilization (LCGU) was analyzed in identical brain structures by application of the quantitative autoradiographic 2-deoxyglucose method to conscious rats. The range of LCGU was from -59% to +55% of the mean. No correlation was found between the moderately heterogeneous Glut3 transporter density and the strongly heterogeneous local cerebral glucose utilization. The results show that the local density of Glut3 glucose transporter protein does not reflect the local level of glucose utilization in the brain.

Animals

The importance of baroreceptor afferents for the decrease in brain glucose utilization during stimulation of the rostroventrolateral medulla of the rat.

The rostroventrolateral medulla (RVLM) is the main integration center for the regulation of the sympathetic outflow. The present study had the aim of investigating the effects of stimulation of the RVLM on the glucose utilization of the brain. Local cerebral glucose utilization (LCGU) can be regarded as an indicator of the brain functional activity. In anesthetized (chloralose-urethan), paralyzed (pancuronium) and ventilated rats, the medulla was exposed by a ventral craniotomy. The RVLM was stimulated by microinjection of 100 nl of 0.5 M sodium glutamate (n = 6). The effective stimulation was verified by the increase in arterial blood pressure. In a control group (n = 7), an identical volume of saline was injected into the RVLM. Local cerebral glucose utilization was measured in both groups using the 2-[14C]deoxyglucose method. The results showed a significant decrease in LCGU in the stimulated group in 33 of 39 brain structures examined. In order to investigate whether the decrease in brain glucose utilization is secondary to the stimulation of baroreceptor afferents by the increase in arterial blood pressure the carotid sinus nerves and both vagal nerves were cut. In this denervated group (n = 5) the decrease in LCGU was abolished in all brain structures although blood pressure was increased to a degree comparable to the innervated group. It is concluded that cerebral glucose metabolism is decreased during stimulation of the RVLM and that this decrease is secondary to the activation of baroreceptor afferents by the increase in blood pressure.

Afferent Pathways

Intracerebroventricular injection of streptozotocin induces discrete local changes in cerebral glucose utilization in rats.

The purpose of the present study was to investigate whether or not cerebral glucose utilization is changed locally after damage of the neuronal insulin receptor by means of intracerebroventricular (icv) streptozotocin (STZ) administered in a subdiabetogenic dosage (1.5 mg/kg bw.). STZ was administered at the start of the study, and 2 and 21 days later bilaterally into the cerebral ventricles in rats of a mean age of 18 months. The local distribution of cerebral glucose utilization was analyzed in conscious rats on the 42nd day after the first STZ injection using the quantitative (14C)-2-deoxyglucose method. Of the 35 brain structures investigated from autoradiograms of brain sections, 17 showed a reduction in glucose utilization. Decreases in glucose utilization were observed in the frontal, parietal, sensory motor, auditory and entorhinal cortex and in all hippocampal subfields. In contrast, glucose utilization was increased in two white matter structures. The decrease in cerebral glucose utilization observed in cortical and hippocampal areas in the present study may correspond to changes in morphobiological parameters which have been found in patients with Alzheimer's disease. The present data are in accordance with the hypothesis that an impairment in the control of neuronal glucose metabolism at the insulin receptor site may exist in sporadic dementia of Alzheimer type (DAT), and can be studied by the icv STZ animal model.

Animals

Changes in brain capillary diameter during hypocapnia and hypercapnia.

Since changes in the surface area of capillaries may be relevant to capillary exchange, the distensibility of brain capillaries was investigated. Brain capillary diameters were measured after perfusion fixation of brain tissue at a constant perfusion pressure during hypo- or hypercapnia. Sections were embedded, stained, and analyzed by light microscopy. The results showed significant differences in mean capillary diameter between the hypocapnic and the hypercapnic group. In the eight brain structures analyzed, capillary diameters were always larger in the hypercapnic group. Mean capillary diameter was 4.93 +/- 0.29 microns in the hypocapnic group and 5.91 +/- 0.10 microns in the hypercapnic group (means +/- SD). We conclude that brain capillaries exhibit a moderate degree of distensibility. Variations in the precapillary pressure of microvessels may therefore influence both capillary flow and capillary surface area.

Animals

[Ultrasound of incidental tumors of the adrenal gland and endocrine hypertension].

We report on a retrospective analysis of 1,500 hypertensive patients who underwent a sonographic examination of the abdomen. 8 'incidentalomas' of the adrenal gland (0.6%) were thereby found. Endocrinological analysis showed that only 1 of the incidentalomas was active (pheochromocytoma). The other tumors had no endocrine activity. On the other side, 7 patients without any sonographic abnormality had hyperaldosteronism, 1 patient suffered from an adrenomedullary hyperplasia. Those patients had been thought to have endocrine hypertension from clinical suspicion. We conclude that a thorough sonographic examination of the adrenal area is an important part of the diagnostic workup in hypertensive patients, although most of the incidentally discovered tumors are endocrinologically inactive. Adrenocortical and adrenomedullary hyperplasias and adrenocortical adenomas are detected clinically while they are still not visible by ultrasound.

Adrenal Gland Neoplasms