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- Carlsson, Ylva, 1975, et al.
(författare)
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Role of mixed lineage kinase inhibition in neonatal hypoxia-ischemia.
- 2009
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 31:5, s. 420-6
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxic-ischemic brain injury is often delayed and involves both apoptotic and immunoregulatory mechanisms. In this study, we used a neonatal model of hypoxia-ischemia to examine the effect of the mixed lineage kinase (MLK) inhibitor CEP-1347 on brain damage, apoptosis and inflammation. The tissue volume loss was reduced by 28% (p = 0.019) in CEP-1347-treated versus vehicle-treated rats and CEP-1347 significantly attenuated microgliosis at 7 days (p = 0.038). CEP-1347 decreased TUNEL-positive staining as well as cleaved caspase 3 immunoreactivity. CEP-1347 did not affect the expression of pro-inflammatory cytokines IL-1 beta, IL-6 and MCP-1, nor did it affect the expression of OX-42 (CR3) and OX-18 (MHC I) 24 h after the insult. In conclusion, the MLK inhibitor CEP-1347 has protective effects in a neonatal rat model of hypoxia-ischemia, which is mainly related to reduced apoptosis.
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| 4. |
- Doverhag, Christina, 1979, et al.
(författare)
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Pharmacological and genetic inhibition of NADPH oxidase does not reduce brain damage in different models of perinatal brain injury in newborn mice
- 2008
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 31:1, s. 133-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation and reactive oxygen species (ROS) are important in the development of perinatal brain injury. The ROS-generating enzyme NADPH oxidase (Nox2) is present in inflammatory cells and contributes to brain injury in adult animal models. HYPOTHESIS: NADPH oxidase contributes to ROS formation and development of injury in the immature brain and inhibition of NADPH oxidase attenuates perinatal brain injury. METHODS: We used animal models of term hypoxia-ischemia (HI) (P9 mice) as well as ibotenate-induced excitotoxic injury (P5 mice) mimicking features of periventricular leukomalacia in preterm infants. In vitro microglia cell cultures were used to investigate NADPH oxidase-dependent ROS formation. In vivo we determined the impact 1) of HI on NADPH oxidase gene expression 2) of genetic (gp91-phox/Nox2 knock-out) and 3) of pharmacological NADPH oxidase inhibition on HI-induced injury and NMDA receptor-mediated excitotoxic injury, respectively. Endpoints were ROS formation, oxidative stress, apoptosis, inflammation and extent of injury. RESULTS: Hypoxia-ischemia increased NADPH oxidase subunits mRNA expression in total brain tissue in vivo. In vitro ibotenate increased NADPH oxidase-dependent formation of reactive oxygen species in microglia. In vivo the inhibition of NADPH oxidase did not reduce the extent of brain injury in any of the animal models. In contrast, the injury was increased by inhibition of NADPH oxidase and genetic inhibition was associated with an increased level of galectin-3 and IL-1beta. CONCLUSION: NADPH oxidase is upregulated after hypoxia-ischemia and activated microglia cells are a possible source of Nox2-derived ROS. In contrast to findings in adult brain, NADPH oxidase does not significantly contribute to the pathogenesis of perinatal brain injury. Results obtained in adult animals cannot be transferred to newborns and inhibition of NADPH oxidase should not be used in attempts to attenuate injury.
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| 5. |
- Eklind, Saskia, et al.
(författare)
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Effect of lipopolysaccharide on global gene expression in the immature rat brain
- 2006
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Ingår i: Pediatr Res. ; 60:2, s. 161-8
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Tidskriftsartikel (refereegranskat)abstract
- To improve the understanding of the molecular mechanisms whereby lipopolysaccharide (LPS) affects the immature brain, global gene expression following LPS exposure was investigated in neonatal rats. Brains (n = 5/time point) were sampled 2, 6, and 72 h after LPS and compared with age-matched controls. The mRNA from each brain was analyzed separately on Affymextrix GeneChip Rat Expression Set 230. The number of genes regulated after LPS were 847 at 2 h, 1564 at 6 h, and 1546 genes at 72 h. Gene ontology analysis demonstrated that, at both 2 and 6 h after LPS, genes associated with protein metabolism, response to external stimuli and stress (immune and inflammatory response, chemotaxis) and cell death were overrepresented. At 72 h, the most strongly regulated genes belonged to secretion of neurotransmitters, transport, synaptic transmission, cell migration, and neurogenesis. Several pathways associated with cell death/survival were identified (caspase-tumor necrosis factor alpha [TNF-alpha]-, p53-, and Akt/phosphatidylinositol-3-kinase (PI3 K)-dependent mechanisms). Caspase-3 activity increased and phosphorylation of Akt decreased 8 h after peripheral LPS exposure. These results show a complex cerebral response to peripheral LPS exposure. In addition to the inflammatory response, a significant number of cell death-associated genes were identified, which may contribute to increased vulnerability of the immature brain to hypoxia-ischemia (HI) following LPS exposure.
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| 6. |
- Ericsson, Jessica S, 1971, et al.
(författare)
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Periodontal health status in Swedish adolescents: an epidemiological, cross-sectional study
- 2009
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Ingår i: Swedish Dental Journal. - 0347-9994. ; 33:(3), s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this epidemiological survey was to analyze the periodontal conditions of 19-year old individuals in two rural county areas, i.e. Fyrbodal and Skaraborg, Västra Götaland, Sweden, with special reference to gender and socioeconomic grouping. A randomized sample of 506 individuals (Fyrbodal 250 and Skaraborg 256 individuals, respectively) was clinically examined with regard to oral hygiene, gingivitis, periodontal pockets and gingival recession. Bitewing radiographs were used for assessment of alveolar bone level (ABL) and dental calculus. A questionnaire-based interview regarding oral hygiene habits was included. A majority of the subjects (76%) claimed to brush their teeth at least twice a day, while interdental hygiene means were used daily by 4%. The subjects showed a mean plaque score of 47% and a gingivitis score of 56%. Forty-six % of the adolescents had a plaque score of > or = 50%, whereas the corresponding figure for gingivitis was 62%. The subjects had on average 5.5 teeth with facial gingival recession. The mean prevalence of sites with probing depth (PPD) of > or = 4 mm was 8, out of which 99% were located at proximal sites. A radiographic bone level of > 2 mm was observed at on average 0.4 teeth per subject. Logistic regression analyses revealed that gender (males) and county area (Fyrbodal) were significant factors for a high plaque and gingivitis score. There was no significant difference in periodontal conditions in relation to socio-economic grouping. In conclusion, the survey revealed higher prevalence of plaque and gingivitis among male than female adolescents, but no differences between socioeconomic groups.
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| 7. |
- Gustafsson Brywe, Katarina, 1965, et al.
(författare)
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IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement of Akt and GSK3beta?
- 2005
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Ingår i: Eur J Neurosci. - : Wiley. - 0953-816X. ; 21:6, s. 1489-502
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor I (IGF-I) is a neurotrophic factor that promotes neuronal growth, differentiation and survival. Neuroprotective effects of IGF-I have previously been shown in adult and juvenile rat models of brain injury. We wanted to investigate the neuroprotective effect of IGF-I after hypoxia-ischemia (HI) in 7-day-old neonatal rats and the mechanisms of IGF-I actions in vivo. We also wanted to study effects of HI and/or IGF-I on the serine/threonine kinases Akt and glycogen synthase kinase 3beta (GSK3beta) in the phophatidylinositol-3 kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and phosphorylated GSK3beta (pGSK3beta) immunoreactivity was lost in the ipsilateral and reduced in the contralateral hemisphere. After 45 min, pAkt levels were restored to control values, whereas pGSK3beta remained low 4 h after HI. Administration of IGF-I (50 microg i.c.v.) after HI resulted in a 40% reduction in brain damage (loss of microtubule-associated protein) compared with vehicle-treated animals. IGF-I treatment without HI was shown to increase pAkt whereas pGSK3beta decreased in the cytosol, but increased in the nuclear fraction. IGF-I treatment after HI increased pAkt in the cytosol and pGSK3beta in both the cytosol and the nuclear fraction in the ipsilateral hemisphere compared with vehicle-treated rats, concomitant with a reduced caspase-3- and caspase-9-like activity. In conclusion, IGF-I induces activation of Akt during recovery after HI which, in combination with inactivation of GSK3beta, may explain the attenuated activation of caspases and reduction of injury in the immature brain.
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| 8. |
- Gustafsson, Nils, et al.
(författare)
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This Time It’s Personal: Social Networks, Viral Politics and Identity Management
- 2009
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Ingår i: The Real and the Virtual. - 9781848880122 ; , s. 35-44
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This paper deals with new forms of political mobilisation and participation in social media. The main focus is on the importance of social networks in providing a “media filter”, functioning as a kind of collective gatekeeper to spread news and information perceived as important, in contrast to the image of the single individual media consumer faced with an insurmountable mass of information. I argue that by investing one’s personal ethos in spreading information and encourage peers in the personal social network to political participation, vital news and calls for action spread quickly. A form of viral politics ensues that, in concordance with traditional types of mediation and formation of political opinion, might provide a basis for a new type of political elite in competitive democracy. Drawing on earlier research concerning the effect of social capital created by weak ties on political participation, I argue that social networks organised online provide a new type of post-organisational weak ties, functioning as maintained social capital building institutions, encouraging to and organising actions of civic engagement. More specifically, a case is made for the need for more thorough conceptualisation of new modes of participation: spontaneous, individualised, “unorganised” forms of action. Two concepts, “temporal elites” and “viral politics” are developed for describing how social network membership and density determine how people are recruited to political campaigns. The theoretical assumptions are further illustrated by the preliminary empirical findings of an ongoing study of Swedish Facebook users and their attitudes and behaviour concerning political participation in social media
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