| 1. |
- Abi-Dargham, A, et al.
(author)
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Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility
- 2000
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In: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X. ; 20:2, s. 225-243
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Journal article (peer-reviewed)abstract
- To evaluate the postulated role of extrastriatal D1 receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [11C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D1 receptor. The goal of this study was to develop and evaluate methods to derive D1 receptor parameters in striatal and extrastriatal regions of the human brain with [11C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient ( k3/ k4). Both kinetic and graphic analyses provided BP and k3/ k4 values in good agreement with the known distribution of D1 receptors (striatum > limbic regions = neocortical regions > thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k3/ k4 by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90 ± 0.06 (mean ± SD of 12 regions) and 0.84 ± 0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72 ± 0.17 and 0.58 ± 0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [11C]NNC 112 uptake provides an appropriate method with which to derive D1 receptor parameters in regions with both high (striatal) and low (extrastriatal) D1 receptor density.
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| 2. |
- Agardh, Carl-David, et al.
(author)
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Hypoglycemic brain injury. I. Metabolic and light microscopic findings in rat cerebral cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration
- 1980
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In: Acta Neuropathologica. - 1432-0533. ; 50:1, s. 31-41
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Journal article (peer-reviewed)abstract
- Profound hypoglycemia causing the disappearance of spontaneous EEG activity was induced by insulin in rats. For analysis of cerebral cortical concentrations of labile phosphates, glycolytic metabolites and amino acids, the brain was frozen in situ. For microscopic analysis of the corresponding cerebral cortical areas the brain was fixed by perfusion. Hypoglycemia with an isoelectric EEG for 30 and 60 min caused severe perturbation of the cerebral energy metabolites. After both 30 and 60 min of isoelectric EEG, two microscopically different types of nerve cell injury were seen. Type I injury was characterized by angulated, darkly stained neurons with perineuronal vacuolation, mainly affecting small neurons in cortical layer 3. Type II injured neurons, mainly larger ones in layers 5–6, were slightly swollen with vacuolation or clearing (depending on the histotechnique used) of the peripheral cytoplasm, but had no nuclear changes. Recovery was induced by glucose injection. Improvement in the cerebral energy state occurred during the 30 min recovery period even after 60 min of hypoglycemia. However, the persisting reduction in the size of adenine nucleotide and amino acid pools after 30 or 180 min recovery suggested that some cells remained damaged. In confirmation many type I injured neurons persisted during the recovery suggesting an irreversible injury. The disappearance of virtually all type II injuries indicated reversibility of these histopathological changes. The microscopic changes in hypoglycemia were different from those in anoxia-ischemia suggesting a dissimilar pathogenesis in these states despite the common final pathway of energy failure.
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| 3. |
- Agardh, Carl-David, et al.
(author)
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Hypoglycemic brain injury: metabolic and structural findings in rat cerebellar cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration
- 1981
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In: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 1:1, s. 71-84
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Journal article (peer-reviewed)abstract
- Previous results have shown that severe, prolonged hypoglycemia leads to neuronal cell damage in, among other structures, the cerebral cortex and the hippocampus but not the cerebellum. In order to study whether or not this sparing of cerebellar cells is due to preservation of cerebellar energy stores, hypoglycemia of sufficient severity to abolish spontaneous EEG activity was induced for 30 and 60 min. At the end of these periods of hypoglycemia, as well as after a 30 min recovery period, cerebellar tissue was sampled for biochemical analyses or for histopathological analyses or for histopathological analyses by means of light and electron microscopy. After 30 min of hypoglycemia. the cerebellar energy state, defined in terms of the phosphocreatine, ATP, ADP, and AMP concentrations, was better preserved than in the cerebral cortex. After 60 min, gross deterioration of cerebellar energy state was observed in the majority of animals, and analyses of carbohydrate metabolites and amino acids demonstrated extensive consumption of endogenous substrates. In spite of this metabolic disturbance, histopathologic alterations were surprisingly discrete. After 30 min, no clear structural changes were observed. After 60 min, only small neurons in the molecular layer (basket cells) were affected, while Purkinje cells and granule cells showed few signs of damage. The results support our previous conclusion that the pathogenesis of cell damage in hypoglycemia is different from that in hypoxia-ischemia and indicate that other mechanisms than energy failure must contribute to neuronal cell damage in the brain.
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| 4. |
- Agardh, Carl-David, et al.
(author)
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Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries
- 2000
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In: Journal of Diabetes and its Complications. - 1873-460X. ; 14:3, s. 146-153
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Journal article (peer-reviewed)abstract
- Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
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| 5. |
- Ahmadi, Khazar, et al.
(author)
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Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease
- 2024
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In: Journal of Neuroscience. - 0270-6474. ; 44:18
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Journal article (peer-reviewed)abstract
- Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.
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| 6. |
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| 7. |
- Ahnstedt, Hilda
(author)
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Stroke, Sex and Vascular Receptor Changes in the Brain
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Stroke is a severe cerebrovascular disease in which the neuronal tissue and vasculature of the brain undergo ischemia-evoked alterations. We have demonstrated an increased expression of cerebrovascular contractile receptors in the brain. This is hypothesized to mitigate cerebral blood flow and exacerbate tissue damage after stroke. An increased contractile property of these receptors has been demonstrated to occur by MEK/ERK1/2 signaling. The majority of pre-clinical studies on stroke are performed in young healthy male animals, despite the fact there is a difference in male and female stroke incidence. The present thesis therefore aimed to investigate the status of vascular receptor changes after experimental stroke and organ culture, with two focus areas that previously have been missing – studies on human material and female subjects. In human cerebral arteries, we found that increased vasoconstriction of 5-HT1B, AT1 and ETB receptors during organ culture, a model of ischemic-like receptor changes, is mediated by B-Raf/MEK/ERK1/2 signaling. Although, increased mRNA and protein of these receptors were found in arteries from both sexes, the contraction to Ang II and ET-1 was markedly lower in female arteries. Focal cerebral ischemia in female rats induced an enhanced contractile property of cerebrovascular ETB receptors, similar to previous observations in males. Ovariectomy, and thereby loss of progesterone and estrogen, resulted in less ischemia-induced ETB receptor upregulation. Hormone therapy with progesterone, but not estrogen, reversed these changes. The increased ETB receptor expression and vasoconstriction after cerebral ischemia in female rat was demonstrated to be mediated by MEK/ERK1/2 signaling. MEK1/2 inhibition attenuated the ETB receptor upregulation and improved the neurological outcome. The present thesis demonstrates for the first time sex differences in vascular function of human cerebral arteries. The underlying mechanism in decreased responsiveness of female arteries remains to be elucidated. This may involve differences in receptor coupling or signal transduction influenced by female sex steroid hormones, or biological sex. Our experimental studies on stroke suggest the loss of progesterone after ovariectomy suppresses ischemia-induced ETB receptor upregulation. Further, the signal transduction pathway involved in vascular receptor changes after cerebral ischemia is suggested to be similar in both sexes. MEK1/2 inhibition is therefore a promising therapeutic target for stroke therapy in both males and females.
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| 8. |
- Akhmediev, N., et al.
(author)
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Cherenkov radiation emitted by solitons in optical fibers
- 1995
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In: Physical Review A - Atomic, Molecular, and Optical Physics. - 2469-9926 .- 2469-9934. ; 51:3, s. 2602-2607
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Journal article (peer-reviewed)abstract
- We demonstrate a simple, fully analytic method of calculating the amount of radiation emitted by optical solitons perturbed by higher-order dispersion effects in fibers and find good agreement with numerical results. It is pointed out that this radiation mechanism is analogous to the well-known Cherenkov radiation processes in nonlinear optics. © 1995 The American Physical Society.
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| 9. |
- Alakula, Mats, et al.
(author)
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ELECTRICAL APPARATUS COMPRISING DRIVE SYSTEM AND ELECTRICAL MACHINE WITH RECONNECTABLE STATOR WINDING
- 2011
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Patent (other academic/artistic)abstract
- Electrical apparatus, comprising a drive system and an electrical machine for propulsion of a vehicle, wherein the electrical machine comprises at least one rotor and at least one stator winding and can be connected via a connection point to a three-phase network. The stator winding can be switched between at least a first position in which it is electrically controlled by the drive system during propulsion of the vehicle, and a second position in which it is divided into at least two separate and magnetically coupled three-phase windings for converting of a voltage level that is available in the three-phase network. One divided first three-phase winding, consisting of a first set of windings, at a rotor speed corresponding to the frequency of the three-phase network has a voltage corresponding to the voltage level at the connection point. One divided second three-phase winding, consisting of a second set of windings, is electrically matched to the drive system and the windings in the first set and the windings in the second set are each connected to each other via a switching layout.
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| 10. |
- Ansal, A., et al.
(author)
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Site Characterization and Site Amplification for a Seismic Microzonation Study in Turkey
- 2004
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Conference paper (peer-reviewed)abstract
- The pilot areas were divided into cells by a grid system of 500 m x 500 m for estimating the effects of site conditions at a scale of 1:5000 by assigning representative soil profiles at the centre of each grid. These soil profiles were classified according to the Turkish Earthquake Code, NEHRP site classification, equivalent shear wave velocity and used for site response analyses. The zonation maps involve the division of the area into three zones as (A, B, and C). In all cases, the variations of the calculated parameters are considered separately and their frequency distributions were determined. Thus the zone A shows the most unsuitable 33 percentile, zone B the medium 34 percentile and zone C shows the most favorable 33 percentile. A suitable pa-rameter is considered to be the average spectral acceleration between 0.5-1.5 sec periods obtained from site response analysis. Even though more empirical, the spectral amplifi-cations calculated using equivalent shear wave velocities gave consistent values that appear to be realistic when compared with the selected soil profiles. Thus microzonation maps with respect to ground shaking were based on the average of spectral accelerations and spectral amplifications obtained from equivalent shear wave velocities.
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