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Mikael Elam

Bio: Mikael Elam is an academic researcher from Sahlgrenska University Hospital. The author has contributed to research in topics: Sympathetic nervous system & Microneurography. The author has an hindex of 48, co-authored 152 publications receiving 6990 citations. Previous affiliations of Mikael Elam include University of Gothenburg & University of Bologna.


Papers
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Journal ArticleDOI
TL;DR: Two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemoragic patients from healthy volunteers are presented.
Abstract: Here, we present two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemorrhagic patients from healthy volunteers. The system was based on microwave scattering measurements with an antenna system worn on the head. Measurement data were analyzed with a machine-learning algorithm that is based on training using data from patients with a known condition. Computer tomography images were used as reference. The detection methodology was evaluated with the leave-one-out validation method combined with a Monte Carlo-based bootstrap step. The clinical motivation for this project is that ischemic stroke patients may receive acute thrombolytic treatment at hospitals, dramatically reducing or abolishing symptoms. A microwave system is suitable for prehospital use, and therefore has the potential to allow significantly earlier diagnosis and treatment than today.

310 citations

Journal ArticleDOI
TL;DR: A selective increase in cardiac adrenergic drive (increased amounts of transmitter available at neuroeffector junctions) in patients with mild-to-moderate CHF appears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF.
Abstract: Background Previous studies with radiotracer methods have indicated increases in cardiac norepinephrine (NE) and renal NE spillover in patients with severe congestive heart failure (CHF). However, data on the regional sympathetic profile in early stages of CHF are limited. In this study, sympathetic function in the heart, kidneys, and skeletal muscle was evaluated in patients with mild-to-moderate CHF and compared with that in patients with severe CHF and healthy subjects. Methods and Results Total body and regional NE spillover from the heart and kidney was assessed with isotope dilution with steady state infusions of [3H]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n=21) was increased threefold versus that in healthy subjects (n=12, P<.05), whereas total body and renal NE spillover and MSA did not differ from those in healthy subjects. In the severe CHF group (n=12), cardiac NE spillover wa...

295 citations

Journal ArticleDOI
TL;DR: The excess of high frequency oscillations may reflect imbalance in the excitation-inhibition homeostasis in the cortex, which may contribute to development of the disorder.

256 citations

Journal ArticleDOI
TL;DR: The results indicate that the previously observed increase in brain NE turnover in hypercapnia is largely secondary to increased neuronal activity and not due to changes in metabolic enzymes, and implicate chemoreceptors, centrally but also peripherally located, in the regulation of brain NE neurons in the LC.

247 citations

Journal ArticleDOI
TL;DR: The results show that the baroreflex mechanisms regulating the occurrence and strength of sympathetic bursts are not identical, and suggest that the modulation occurs at two sites, one which determines whether or not a burst will occur, and another at which the strength of the discharge is determined.
Abstract: Human muscle sympathetic activity (MSA) is modulated by arterial baroreflex mechanisms: the sympathetic impulses are grouped in pulse synchronous bursts occurring preferentially during transient reductions of blood pressure (Delius et al. 1972), and changes in arterial baroreceptor firing induce reciprocal changes in the strength of the MSA (Wallin et al. 1975; Wallin & Eckberg, 1982). In each subject an approximately constant baroreflex latency can be defined, i.e. a given sympathetic burst can always be related to a given cardiac cycle (Delius et al. 1972). This basic relationship is similar in all subjects despite the fact that some subjects have few, and others many, sympathetic bursts. Such interindividual differences in the amount of activity are highly reproducible over several years (Sundlof & Wallin, 1977; Fagius & Wallin, 1993). Different methods have been used to quantify the arterial baroreflex influence on MSA. In an early study, Sundlof & Wallin (1978) described the relationship between spontaneous variations of blood pressure and nerve traffic in terms of (1) threshold (i.e. whether or not a sympathetic burst is generated) and (2) baroreflex sensitivity (i.e. the slope of the relationship between the strength of a burst and the diastolic pressure in the corresponding heart beat). The same approach has been used to study baroreflex sensitivity during sleep (Nakazato et al. 1998) and to compare groups of normotensive and hypertensive subjects (Wallin & Sundlof, 1979). More commonly, baroreflex effects on MSA have been quantified by measuring the relationship between changes in MSA and blood pressure induced by injections of vasoactive drugs. This approach has been used to study baroreflex sensitivity in healthy subjects at different ages (e.g. Ebert et al. 1992; Matsukawa et al. 1996), in association with manoeuvres (e.g. Halliwill et al. 1996), in cardiovascular diseases (e.g. Ferguson et al. 1992; Grassi et al. 1995; Carlson et al. 1996; Meyrelles et al. 1997) or after administration of anaesthetic drugs (e.g. Sellgren et al. 1994; Muzi & Ebert, 1995). Surprisingly, neither method has been used to quantify arterial baroreflex characteristics in individual subjects. Thus, it is not known whether significant arterial baroreflex thresholds and sensitivites in MSA can be defined for all subjects, and whether, in a given subject, such measures of arterial baroreflex function are reproducible. It is also unknown whether baroreflex characteristics in MSA differ between subjects with few and many MSA bursts at rest. The aim of the present study was to answer these questions. Baroreflex threshold and sensitivity were determined from spontaneous variations of blood pressure/cardiac interval and sympathetic nerve traffic (Sundlof & Wallin, 1978). To minimize random variations in the results, a study of the method of analysis was also included.

246 citations


Cited by
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Journal ArticleDOI
06 Jun 1986-JAMA
TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.
Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

7,563 citations

Journal ArticleDOI
16 Oct 2009-Cell
TL;DR: Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.

3,394 citations

Journal ArticleDOI
04 Jun 2009-Nature
TL;DR: The timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses and provided the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.
Abstract: Corticalgammaoscillations(20280Hz)predictincreasesinfocusedattention,andfailureingammaregulationisahallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons atvariedfrequencies (82200Hz) selectivelyamplifies gamma oscillations. Incontrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.

2,453 citations

Journal ArticleDOI
04 Jun 2009-Nature
TL;DR: Optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.
Abstract: Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin have been suggested to be involved in gamma (30-80 Hz) oscillations, which are hypothesized to enhance information processing. However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia and autism). Here we use a panel of optogenetic technologies in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.

2,383 citations

Journal Article
TL;DR: The activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages.
Abstract: The brain and the immune system are the two major adaptive systems of the body During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome

2,030 citations