| 1. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
-
Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
-
Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
|
|
| 2. |
- Björnsdotter, Malin, et al.
(författare)
-
A Monte Carlo method for locally multivariate brain mapping.
- 2011
-
Ingår i: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119.
-
Tidskriftsartikel (refereegranskat)abstract
- Locally multivariate approaches to functional brain mapping offer a highly appealing complement to conventional statistics, but require restrictive region-of-interest hypotheses, or, in exhaustive search forms (such as the "searchlight" algorithm; Kriegeskorte et al., 2006), are excessively computer intensive. We therefore propose a non-restrictive, comparatively fast yet highly sensitive method based on Monte Carlo approximation principles where locally multivariate maps are computed by averaging across voxelwise condition-discriminative information obtained from repeated stochastic sampling of fixed-size search volumes. On simulated data containing discriminative regions of varying size and contrast-to-noise ratio (CNR), the Monte Carlo method reduced the required computer resources by as much as 75% compared to the searchlight with no reduction in mapping performance. Notably, the Monte Carlo mapping approach not only outperformed the general linear method (GLM), but also produced higher discriminative voxel detection scores than the searchlight irrespective of classifier (linear or nonlinear support vector machine), discriminative region size or CNR. The improved performance was explained by the information-average procedure, and the Monte Carlo approach yielded mapping sensitivities of a few percent lower than an information-average exhaustive search. Finally, we demonstrate the utility of the algorithm on whole-brain, multi-subject functional magnetic resonance imaging (fMRI) data from a tactile study, revealing that the central representation of gentle touch is spatially distributed in somatosensory, insular and visual regions.
|
|
| 3. |
- Gray, Marcus A, et al.
(författare)
-
Following one's heart: cardiac rhythms gate central initiation of sympathetic reflexes.
- 2009
-
Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 29:6, s. 1817-25
-
Tidskriftsartikel (refereegranskat)abstract
- Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety.
|
|
| 4. |
- Olausson, Håkan, 1965, et al.
(författare)
-
Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.
- 2008
-
Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - : Springer Science and Business Media LLC. - 1432-1106. ; 184:1, s. 135-40
-
Tidskriftsartikel (refereegranskat)abstract
- In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects' ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.
|
|
| 5. |
- Olausson, Håkan, 1965, et al.
(författare)
-
Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing.
- 2008
-
Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 436:2, s. 128-32
-
Tidskriftsartikel (refereegranskat)abstract
- A previous functional magnetic resonance imaging (fMRI) study of an A-beta deafferented subject (GL) showed that stimulation of tactile C afferents (CT) activates insular cortex whereas no activation was seen in somatosensory cortices. Psychophysical studies suggested that CT afferents contribute to affective but not to discriminative aspects of tactile stimulation. We have now examined cortical processing following CT stimulation in a second similarly deafferented subject (IW), as well as revisited the data from GL. The results in IW showed similar activation of posterior insular cortex following CT stimulation as in GL and so strengthen the view that CT afferents underpin emotional aspects of touch. In addition, CT stimulation evoked significant fMRI deactivation in somatosensory cortex in both subjects supporting the notion that CT is not a system for discriminative touch.
|
|
| 6. |
- Rylander, Karin, 1977
(författare)
-
Thin-fibre signalling in humans: Cortical processing of sensory afference and autonomic efference
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thin nerve fibres innervate the entire human body and mediate sensations such as pain, temperature and visceral sensory input. Moreover, a special class of unmyelinated afferents responsive to light touch has recently been found in humans: C-tactile (CT) fibres. In the efferent side, C-fibres are the path for signalling in the autonomic nervous system, controlling the internal milieu of the body. There is growing evidence that C-fibres form the basis for monitoring and regulating the physical status of the body. This thesis focuses on central projections of mild thin-fibre input and their integration with autonomic reactions. Brain activity was studied with functional magnetic resonance imaging (fMRI). The first paper examined cortical activation of selective CT-stimulation by soft tactile stimulation in two rare patients lacking Aβ fibres. The results confirmed previous findings based on one of these patients, showing that CT stimulation activates the insular cortex. In addition, CT stimulation deactivated somatosensory cortices. The second paper further investigated cortical effects of CT stimulation in healthy controls by comparing rapid vibration (predominantly activating Aβ fibres) and soft brush stroking (combined Aβ and CT activation) on the skin. The ventromedial prefrontal cortex was significantly more activated by brushing than by vibration, an area previously implied in coding for the expected emotional value of an event. The third paper focused on the role of CT fibres and autonomic function. We again studied the two Aβ deafferented patients to examine whether CT stimulation could evoke an autonomic response. We also examined their ability to localise the CT stimulations to the correct limb. Capacity for localisation of the stimulus was poor but above chance. Despite producing only a vague percept in the patients, the CT stimulus gave rise to a skin sympathetic reaction which was indexed by a galvanic skin response. The fourth paper studied the cortical mechanisms behind a restricted autonomic response elicited by a perceptually weak C-fibre input in healthy subjects. We used low-intensity rectal distension while recording autonomic variables and cortical responses. Rectal distension activated insular cortex. Central activation specifically related to the skin sympathetic response was, in addition to the brainstem, limited to the right inferior frontal gyrus (IFG). The CT evoked insular activation and the Aβ-denervated patients’ poor ability to localise a CT stimulation support the concept that these fibres underpin affective rather than discriminative aspects of touch. The rectal distension study indicated that insular activation via low-threshold mechanovisceral thin fibres predominantly reflects afferent processing whereas IFG and the brainstem may be important in the generation of autonomic responses. Further, the studies suggest that stimulus perception is a prerequisite for cutaneous autonomic responses to both CT and visceral thin fibre stimuli. These findings set the stage for future studies of thin nerve fibre function, including neural mechanisms of hedonic processing as well as pathophysiological studies of conditions such as irritable bowel syndrome, which may tease out putative contributions from afferent input, cognitive processing and autonomic consequences.
|
|
