| 21. |
- Quattromani, Miriana Jlenia, et al.
(författare)
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Changes in resting-state functional connectivity after stroke in a mouse brain lacking extracellular matrix components
- 2018
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 112, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- In the brain, focal ischemia results in a local region of cell death and disruption of both local and remote functional neuronal networks. Tissue reorganization following stroke can be limited by factors such as extracellular matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The brain's ECM plays a crucial role in network formation, development, and regeneration of the central nervous system. Further, the ECM is essential for proper white matter tract development and for the formation of structures called perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory interneurons, of importance for processing sensory information. Previous studies have shown that downregulating PNNs after stroke reduces the neurite-inhibitory environment, reactivates plasticity, and promotes functional recovery. Resting-state functional connectivity (RS-FC) within and across hemispheres has been shown to correlate with behavioral recovery after stroke. However, the relationship between PNNs and RS-FC has not been examined. Here we studied a quadruple knock-out mouse (Q4) that lacks four ECM components: brevican, neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and 14 days after photothrombotic stroke (PT) to understand how the lack of crucial ECM components affects neuronal networks and functional recovery after stroke. Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC compared to wild-type mice, especially in the sensory and parietal regions. Changes in RS-FC were significantly correlated with the number of interhemispheric callosal crossings in those same regions. PT caused unilateral damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing ability in contralesional fore- and hindlimbs, but the two experimental groups did not present significant differences in infarct size. Two weeks after PT, a general down-scaling of regional RS-FC as well as the number of regional functional connections was visible for all cortical regions and most notable in the somatosensory areas of both Q4 and wild-type mice. Q4 mice exhibited higher intrahemispheric RS-FC in contralesional sensory and motor cortices compared to control mice. We propose that the lack of growth inhibiting ECM components in the Q4 mice potentially worsen behavioral outcome in the early phase after stroke, but subsequently facilitates modulation of contralesional RS-FC which is relevant for recovery of sensory motor function. We conclude that Q4 mice represent a valuable model to study how the elimination of ECM genes compromises neuronal function and plasticity mechanisms after stroke.
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| 22. |
- Rattik, Sara, et al.
(författare)
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IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice.
- 2015
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 242:2, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe(-/-) mice.
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| 23. |
- Rauch, Uwe
(författare)
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Brain matrix: structure, turnover and necessity.
- 2007
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 35:4, s. 656-660
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Tidskriftsartikel (refereegranskat)abstract
- Aided by mice with multiple deleted brain matrix protein genes, the biochemical analysis of mouse brain matrix molecules indicates a constitutive production of more proteoglycans than can be integrated in multimolecular matrix structures. Possible functions of non-matrix integrated proteoglycans, and aspects of incomplete compensatory mechanisms in knockout mice are discussed.
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| 24. |
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| 25. |
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| 26. |
- Rauch, Uwe
(författare)
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Detection of neurocan in cerebrospinal fluid.
- 2012
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1940-6029. ; 836, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CFS) is the most easily accessible component of the human central nervous system and has been successfully used for the analysis of disease-associated molecular imbalances, particularly for extracellular matrix components. Alterations in the presence of the nervous system-associated chondroitin sulfate proteoglycan neurocan had been reported from active multiple sclerosis lesions. Neurocan could be detected as a component of human CFS after enrichment of proteoglycans by anion exchange chromatography from pooled liquor as well as individual 300 μL samples by Western blot. However, a general alteration in neurocan levels in CFS sample with high immunoglobulin content could not be demonstrated. To further reduce the sample size, the development of a PG capturing assay based on polybrene-coated 96-well plates was initiated. This approach could be an interesting alternative option for the analysis of PGs in biological fluid and tissue samples.
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| 27. |
- Rauch, Uwe, et al.
(författare)
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Distinctive peri-luminal presence of agrin in murine and human carotid atherosclerotic plaques
- 2018
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Ingår i: Histology and Histopathology. - 0213-3911. ; 33:7, s. 717-726
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Tidskriftsartikel (refereegranskat)abstract
- The clinical consequences of arterial atherosclerotic lesions depend, apart from their size, on their composition of cellular and extracellular components. While an intact endothelium at the interface of atherosclerotic plaques towards the blood can prevent its erosion, underlying smooth muscle cells within the plaque can reduce the risk of plaque ruptures, due to the deposition of stabilizing extracellular matrix. Basement membranes underlay and support the function of endothelial cells, and embed smooth muscle cells in the media, the source of most smooth muscle cells within atherosclerotic plaques. In the present study mouse atherosclerotic plaques were comparatively analyzed for the basement membrane components laminin, type IV collagen, perlecan, and agrin. Distinct agrin immunofluorescence was found in the peri-luminal area in mouse carotid atherosclerotic plaques. Agrin was also clearly present in the media, with a significant increase in regions directly associated with plaque tissue. In addition, ten human endarterectomy specimens were investigated for this heparan sulfate proteoglycan. No statistically significant differences in agrin immunofluorescence were noticed between five specimens from symptomatic and five from asymptomatic patients. In all these plaques agrin was present in a distinctive manner in a narrow zone partially or almost completely surrounding the lumen. Additionally it was also present around the small lumina of the CD31-positive neovessels. The presence of agrin at locations with particular importance for the growth and stability of atherosclerotic plaques renders this molecule strategically positioned to influence plaque development and vulnerability.
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| 28. |
- Rauch, Uwe, et al.
(författare)
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Extracellular matrix alterations in brains lacking four of its components.
- 2005
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 328:2, s. 608-617
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Tidskriftsartikel (refereegranskat)abstract
- Abstract is not available. This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription.
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| 29. |
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| 30. |
- Rauch, Uwe, et al.
(författare)
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Increased Neointimal Thickening in Dystrophin-Deficient mdx Mice.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The dystrophin gene, which is mutated in Duchenne muscular dystrophy (DMD), encodes a large cytoskeletal protein present in muscle fibers. While dystrophin in skeletal muscle has been extensively studied, the function of dystrophin in vascular smooth muscle is less clear. Here, we have analyzed the role of dystrophin in injury-induced arterial neointima formation. METHODOLOGY/PRINCIPAL FINDINGS: We detected a down-regulation of dystrophin, dystroglycan and β-sarcoglycan mRNA expression when vascular smooth muscle cells de-differentiate in vitro. To further mimic development of intimal lesions, we performed a collar-induced injury of the carotid artery in the mdx mouse, a model for DMD. As compared with control mice, mdx mice develop larger lesions with increased numbers of proliferating cells. In vitro experiments demonstrate increased migration of vascular smooth muscle cells from mdx mice whereas the rate of proliferation was similar in cells isolated from wild-type and mdx mice. CONCLUSIONS/SIGNIFICANCE: These results show that dystrophin deficiency stimulates neointima formation and suggest that expression of dystrophin in vascular smooth muscle cells may protect the artery wall against injury-induced intimal thickening.
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