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  • Forsberg, A., et al. (författare)
  • The Immune Response of the Human Brain to Abdominal Surgery
  • 2017
  • Ingår i: Annals of Neurology. - : WILEY. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
  • Gustafsson, David, et al. (författare)
  • Boreal forest surface parameterization in the ECMWF model - 1D test with NOPEX long-term data
  • 2003
  • Ingår i: Journal of applied meteorology (1988). - : American Meteorological Society. - 0894-8763 .- 1520-0450. ; 42:1, s. 95-112
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the present study was to assess the performance and recent improvements of the land surface scheme used operationally in the European Centre for Medium-Range Weather Forecasts (ECMWF) in a Scandinavian boreal forest climate/ecosystem. The previous (the 1999 scheme of P. Viterbo and A. K. Betts) and the new (Tiled ECMWF Surface Scheme for Exchange Processes over Land, TESSEL) surface schemes were validated by single-column runs against data from NOPEX (Northern Hemisphere Climate-Processes Land-Surface Experiment). Driving and validation datasets were prepared for a 3-yr period (1994-96). The new surface scheme, with separate surface energy balances for subgrid fractions (tiling), improved predictions of seasonal as well as diurnal variation in surface energy fluxes in comparison with the old scheme. Simulated wintertime evaporation improved significantly as a consequence of the introduced additional aerodynamic resistance for evaporation from snow lying under high vegetation. Simulated springtime evaporation also improved because the limitation of transpiration in frozen soils was now accounted for. However, downward sensible heat flux was still underestimated during winter, especially at nighttime, whereas soil temperatures were underestimated in winter and overestimated in summer. The new scheme also underestimated evaporation during dry periods in summer, whereas soil moisture was overestimated. Sensitivity tests showed that further improvements of simulated surface heat fluxes and soil temperatures could be obtained by calibration of parameters governing the coupling between the surface and the atmosphere and the ground heat flux, and parameters governing the water uptake by the vegetation. Model performance also improved when the seasonal variation in vegetation properties was included.
  • Lundin, Lars-Christer, et al. (författare)
  • Continuous long-term measurements of soil-plant-atmosphere variables at a forest site
  • 1999
  • Ingår i: Agricultural and Forest Meteorology. - 0168-1923 .- 1873-2240. ; 98-99, s. 53-73
  • Tidskriftsartikel (refereegranskat)abstract
    • It is a major challenge in modem science to decrease the uncertainty in predictions of global climate change. One of the largest uncertainties in present-day global climate models resides with the understanding of processes in the soil-vegetation-atmosphere-transfer (SVAT) system. Continuous, long-term data are needed in order to correctly quantify balances of water, energy and CO2 in this system and to correctly model it. It is the objective of this paper to demonstrate how a combined system of existing sensor, computer, and network technologies could be set up to provide continuous and reliable long-term SVAT-process data from a forested site under almost all environmental conditions. The Central Tower Site (CTS) system was set up in 1993-1994 in a 25 m high boreal forest growing on a highly heterogeneous till soil with a high content of stones and blocks. It has successfully monitored relevant states and fluxes in the system, such as atmospheric fluxes of momentum, heat, water vapour and CO2, atmospheric profiles of temperature, water vapour, CO2, short-and long-wave radiation, heat storage in soil and trees, sap-dow and a variety of ecophysiological properties, soil-water contents and tensions, and groundwater levels, rainfall and throughfall. System uptime has been more than 90% for most of its components during the first 5 years of operation. Results from the first 5 years of operation include e.g., budgets for energy, water and CO2, information on important but rarely occurring events such as evaporation from snow-covered canopies, and reactions of the forest to extreme drought. The carbon budget shows that the forest may be a sink of carbon although it is still growing. The completeness of the data has made it possible to test the internal consistency of SVAT models. The pioneering set-up at the CTS has been adopted by a large number of SVAT-monitoring sites around the world. Questions concerning tower maintenance, long-term calibration plans, maintenance of sensors and data-collection system, and continuous development of the computer network to keep it up to date are, however, only partly of interest as a research project in itself. It is thus difficult to get it funded from usual research-funding agencies. The full value of data generated by the CTS system can best be appreciated after a decade or more of continuous operation. Main uses of the data would be to evaluate how SVAT models handle the natural variability of climate conditions, quantification of water. carbon and energy budgets during various weather conditions, rind development of new parameterisation schemes in global and regional climate models. 
  • Albrecht, Daniel S., et al. (författare)
  • Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation
  • 2019
  • Ingår i: Brain, behavior, and immunity. - 0889-1591 .- 1090-2139. ; 75, s. 72-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
  • Braniste, Viorica, et al. (författare)
  • The gut microbiota influences blood-brain barrier permeability in mice
  • 2014
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 6:263, s. 263ra158-
  • Tidskriftsartikel (refereegranskat)abstract
    • Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.
  • Cervenka, Simon, et al. (författare)
  • Association between striatal and extrastriatal dopamine D2-receptor binding and social desirability
  • 2010
  • Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 50:1, s. 323-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on the biological underpinnings of personality can provide leads to the pathophysiology of psychiatric disorders. In particular, interpersonal aspects of behavior are a common problem during the course of psychiatric illness. Animal research has demonstrated a role for the dopamine system in social behaviour, and recent molecular imaging studies have shown a negative correlation between dopamine D2-receptor binding in the striatum and social desirability. The emotional and cognitive aspects of social behavior suggest involvement of brain regions outside of the striatum, such as limbic structures. The aim of the present study was to explore associations between the personality trait social desirability and dopamine D2-receptor binding in both striatal and extrastriatal brain regions. We examined 16 control subjects with Positron Emission Tomography and the radioligands [C-11]raclopride and [C-11]FLB 457, in relation to social desirability in the inventory Swedish universities Scales of Personality. [C-11]raclopride D2-receptor binding in the striatum showed negative correlations to social desirability scores, corroborating previous findings. Furthermore, a correlation of a higher statistical significance was demonstrated for [C-11]FLB 457 binding in the hippocampal-amygdala complex. A separate analysis of social desirability items in relation to a model of interpersonal behaviour revealed that the associations were driven by items reflecting high submissiveness and high affiliation. Taken together with previous evidence on D2-receptor binding and social behaviour, a role for dopaminergic neurotransmission in regulating displays of dominance vs. submissive behaviour is proposed. (C) 2009 Elsevier B.V. All rights reserved.
  • Cervenka, Simon, et al. (författare)
  • Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum
  • 2008
  • Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 40:3, s. 1287-1295
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on pharmacological, neuroanatomical, and lesion studies in animals, a functional compartmentalization of the striatal complex has been proposed. However, this has not been convincingly demonstrated in human subjects. Most functions ascribed to the striatum have been linked to its dense dopaminergic innervation, from motor control to higher-order brain functions ( e. g., cognition), making the dopamine system a suitable probe for striatal function. Limbic striatum, a region involved in reward processing, has recently been implicated also in episodic memory function. Here we examined striatal dopamine D2-receptor binding in 16 healthy subjects using PET and the radioligand [C-11] raclopride, in relation to cognitive performance. Receptor availability in limbic striatum was related to performance in tests of episodic memory, but not to tests of verbal fluency and general knowledge. By contrast, D2 binding in associative and sensorimotor striatum was less strongly related to episodic memory, but showed associations to the non-episodic tasks. These findings provide biochemical evidence for a functional compartmentalization of human striatum, and serve as a starting point for a more detailed investigation of striatal biomarkers in the normal brain as well as in neurodegenerative disorders. (c) 2008 Elsevier Inc. All rights reserved.
  • Cervenka, Simon, et al. (författare)
  • PET Studies of D2-Receptor Binding in Striatal and Extrastriatal Brain Regions : Biochemical Support In Vivo for Separate Dopaminergic Systems in Humans
  • 2010
  • Ingår i: Synapse. - : WILEY. - 0887-4476 .- 1098-2396. ; 64:6, s. 478-485
  • Tidskriftsartikel (refereegranskat)abstract
    • Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [C-11]raclopride and [C-11]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.
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