| 1. |
- Bergmark, Ulrika, et al.
(författare)
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Ett forsknings- och utvecklingsteams arbete i uppstarten : en balansgång mellan behov, krav och förväntningar
- 2023
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Ingår i: Forskning och utveckling i förskola och skola. - Piteå : Piteå kommun. - 2004-3635. ; 2:1, s. 32-48
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Tidskriftsartikel (refereegranskat)abstract
- I Piteå kommun bildades i januari 2022 ett forsknings- och utvecklingsteam (FoU-teamet) bestående av kommunens vetenskapliga ledare och fyra förvaltningsövergripande förstelärare. Teamet tillsattes för att arbeta med forskning och utveckling (FoU) i kommunens grundskolor och gymnasier och utgjorde ett led i Utbildningsförvaltningens strävan att förverkliga Skollagens krav om en utbildning på vetenskaplig grund och beprövad erfarenhet (SFS 2010:800). Denna artikel bygger på en studie av FoU-teamets uppstartsfas: de utmaningar som teamet mötte under den första terminen och de lärdomar som gjordes. För att förstå de olika kontexter som var centrala för teamets arbete användes ett policy enactment-perspektiv (Braun et al., 2011). Data samlades in genom att teammedlemmarna och en inbjuden medforskare reflekterade skriftligt samt genomförde fokusgruppsamtal. De utmaningar som framträder i materialet rör tre teman: Öppenhet och styrning i uppdraget, Strategiskt och operativt arbete samt Bredd och djup i aktiviteterna. Lärdomar som drogs var att det behövs tydliga men samtidigt flexibla strukturer, både långsiktigt och kortsiktigt perspektiv samt att förankrings- arbete är viktigt. En central slutsats är att teamet, för att hantera utmaningarna, har gått balansgång och navigerat mellan interna och externa behov, krav och förväntningar på teamets arbete.
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| 2. |
- Bergmark, Ulrika, 1973-, et al.
(författare)
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Ett forsknings- och utvecklingsteams arbete i uppstarten – en balansgång mellan behov, krav och förväntningar
- 2023
-
Ingår i: Forskning & utveckling i förskola och skola (Fufos). - Piteå : Utbildningsförvaltningen Piteå kommun. - 2004-3635. ; 2:1, s. 32-48
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- I Piteå kommun bildades i januari 2022 ett forsknings- och utvecklingsteam (FoU-teamet) bestående av kommunens vetenskapliga ledare och fyra förvaltningsövergripande förstelärare. Teamet tillsattes för att arbeta med forskning och utveckling (FoU) i kommunens grundskolor och gymnasier och utgjorde ett led i Utbildningsförvaltningens strävan att förverkliga Skollagens krav om en utbildning på vetenskaplig grund och beprövad erfarenhet (SFS 2010:800). Denna artikel bygger på en studie av FoU-teamets uppstartsfas: de utmaningar som teamet mötte under den första terminen och de lärdomar som gjordes. För att förstå de olika kontexter som var centrala för teamets arbete användes ett policy enactment-perspektiv (Braun et al., 2011). Data samlades in genom att teammedlemmarna och en inbjuden medforskare reflekterade skriftligt samt genomförde fokusgruppsamtal. De utmaningar som framträder i materialet rör tre teman: Öppenhet och styrning i uppdraget, Strategiskt och operativt arbete samt Bredd och djup i aktiviteterna. Lärdomar som drogs var att det behövs tydliga men samtidigt flexibla strukturer, både långsiktigt och kortsiktigt perspektiv samt att förankringsarbete är viktigt. En central slutsats är att teamet, för att hantera utmaningarna, har gått balansgång och navigerat mellan interna och externa behov, krav och förväntningar på teamets arbete.
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| 3. |
- Block, Linda, et al.
(författare)
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A new concept affecting restoration of inflammation-reactive astrocytes.
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 250, s. 536-45
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Tidskriftsartikel (refereegranskat)abstract
- Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.
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| 4. |
- Block, Linda, et al.
(författare)
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Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2+) signaling in lipopolysaccharide pretreated astrocytes.
- 2012
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 205, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca(2+) responses. EM-1 stimulated the μ-opioid receptor from 10(-15) M up to 10(-4) M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca(2+) responses. However, a combination of ultralow concentration naloxone (10(-12) M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca(2+) responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca(2+) transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca(2+) transients were oscillated. To restore the EM-1-evoked Ca(2+) transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca(2+) transients.
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| 5. |
- Block, Linda, et al.
(författare)
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Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes.
- 2013
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Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 38:11, s. 3669-3678
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Tidskriftsartikel (refereegranskat)abstract
- Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na(+) channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, <10(-8) m, evoked Ca(2+) transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca(2+) signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, <10(-8) m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca(2+) signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist.
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| 6. |
- Delbro, Dick, 1950, et al.
(författare)
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In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments.
- 2009
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 159:2, s. 770-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether nicotine acetylcholine receptors (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with microvascular endothelial cells from adult rat brain, compared with monocultured astrocytes, as a sign of a more developed signal transduction system. Also investigated was whether nicotine plays a role in the control of neuroinflammatory reactivity in astrocytes. Ca(2+) imaging experiments were performed using cells loaded with the Ca(2+) indicator Fura-2/AM. Co-cultured astrocytes responded to lower concentrations of nicotine than did monocultured astrocytes, indicating that they are more sensitive to nicotine. Co-cultured astrocytes also expressed a higher selectivity for alpha7nAChR and alpha4/beta2 subunits and evoked higher Ca(2+) transients compared with monocultured astrocytes. The Ca(2+) transients referred to are activators of Ca(2+)-induced Ca(2+) release from intracellular stores, both IP(3) and ryanodine, triggered by influx through receptor channels. The nicotine-induced Ca(2+) transients were attenuated after incubation with the inflammatory mediator lipopolysaccharide (LPS), but were not attenuated after incubation with the pain-transmitting peptides substance P and calcitonin-gene-related peptide, nor with the infection and inflammation stress mediator, leptin. Furthermore, LPS-induced release of interleukin-1beta (IL-1beta) measured by enzyme-linked immunosorbent assay (ELISA) was more pronounced in co-cultured versus monocultured astrocytes. Incubation with both LPS and IL-1beta further attenuated nicotine-induced Ca(2+) response. We also found that LPS and IL-1beta induced rearrangement of the F-actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The rearrangements consisted of increases in ring formations and a more dispersed appearance of the filaments. These results indicate that there is a connection between a dysfunction of nicotine Ca(2+) signaling in inflammatory reactive astrocytes and upregulation of IL-1beta and the rearrangements of actin filaments in the cells.
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| 7. |
- Forshammar, Johan, et al.
(författare)
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Anti-inflammatory substances can influence some glial cell types but not others.
- 2013
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Ingår i: Brain research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1539, s. 34-40
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Tidskriftsartikel (refereegranskat)abstract
- In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied cytokine release after exposure with 1ng/ml LPS for 0.5-24h. Dexamethasone and corticosterone exposure served as controls. We focused on whether naloxone, ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on astrocytes, could affect the release of TNF-α and IL-1β in microglia. Our results show that neither ultralow (10(-12)M) nor high (10(-6)M) concentrations of these agents had demonstrable effects on cytokine release in microglia. The results indicate that anti-inflammatory substances exert specific influences on different glial cell types. Astrocytes seem to be functional targets for anti-inflammatory substances while microglia respond directly to inflammatory stimuli and are thus more sensitive to anti-inflammatory substances like corticoids. The physiological relevance might be that astrocyte dysfunction influences neuronal signalling both due to direct disturbance of astrocyte functions and in the communication within the astrocyte networks. When the signalling between astrocytes is working, then microglia produce less pro-inflammatory cytokines.
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| 8. |
- Hansson, Elisabeth, 1955, et al.
(författare)
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PACAP attenuates 5-HT, histamine, and ATP-evoked Ca2+ transients in astrocytes.
- 2009
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Ingår i: Neuroreport. - 1473-558X. ; 20:10, s. 957-62
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective properties and plays an important role in neuroinflammation. PACAP38 interacts with its receptors, PAC1, and VPAC, on astrocytes at 10(-8) M to induce biphasic Ca2+ transients, which were reduced to a single transient by the PAC1-blocking PACAP antagonist PACAP6-38. At 10(-12) M even the single transient, corresponding to PAC1 was blocked. PACAP-induced Ca2+ transients were more pronounced in astrocytes cocultured with brain endothelial cells than in monocultured astrocytes, indicating that astrocytes that receive signals from microvessels develop more sensitive signal transduction systems for Ca. In this sensitive system, PACAP38 attenuated 5-HT, histamine, and ATP-evoked Ca2+ transients, showing the anti-inflammatory properties of PACAP.
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| 9. |
- Hansson, Elisabeth, 1955, et al.
(författare)
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μ-Opioid agonists inhibit the enhanced intracellular Ca2+ responses in inflammatory activated astrocytes co-cultured with brain endothelial cells
- 2008
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 155:4, s. 1237-1249
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Tidskriftsartikel (refereegranskat)abstract
- In order to imitate the in vivo situation with constituents from the blood–brain barrier, astrocytes from newborn rat cerebral cortex were co-cultured with adult rat brain microvascular endothelial cells. These astrocytes exhibited a morphologically differentiated appearance with long processes. 5-HT, synthetic μ-, δ- or κ-opioid agonists, and the endogenous opioids endomorphin-1, β-endorphin, and dynorphin induced higher Ca2+ amplitudes and/or more Ca2+ transients in these cells than in astrocytes in monoculture, as a sign of more developed signal transduction systems. Furthermore, stimulation of the co-cultured astrocytes with 5-HT generated a pronounced increase in intracellular Ca2+ release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca2+ responses were restored by opioids so that the δ- and κ-opioid receptor agonists reduced the number of Ca2+ transients elicited after incubation in substance P+CGRP or leptin, while the μ- and δ-opioid receptor agonists attenuated the Ca2+ amplitudes elicited in the presence of LPS or leptin. In LPS treated co-cultured astrocytes the μ-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca2+ transients. These results suggest that opioids, especially μ-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with μ-opioid receptors, also may act through some binding site on astrocytes, other than the classical opioid receptor.
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| 10. |
- Lundborg, Christopher, 1965, et al.
(författare)
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Ifenprodil restores GDNF-evoked Ca(2+) signalling and Na(+) /K(+) -ATPase expression in inflammation-pretreated astrocytes.
- 2011
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Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 119:4, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) plays an important role in neuroinflammatory and neuropathic pain conditions. Astrocytes produce and secrete GDNF, which interacts with its receptors to induce Ca(2+) transients. This study aimed first to assess intracellular Ca(2+) responses of astrocytes in primary culture when exposed to the neuroprotective and anti-inflammatory peptide GDNF. Furthermore, incubation with the inflammatory inducers lipopolysaccharide (LPS), NMDA, or interleukin 1-β (IL-1β) attenuated the GDNF-induced Ca(2+) transients. The next aim was to try to restore the suppressed GDNF responses induced by inflammatory changes in the astrocytes with an anti-inflammatory substance. Ifenprodil, an NMDA receptor antagonist at the NR2B subunit, was tested. It was shown to restore the GDNF-evoked Ca(2+) transients and increased the Na(+) /K(+) -ATPase expression. Ifenprodil seems to be a potent anti-inflammatory substance for astrocytes which have been pre-activated by inflammatory stimuli.
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