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| 2. |
- Nyberg, J, et al.
(författare)
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Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation
- 2005
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - : Society for Neuroscience. - 1529-2401. ; 25:7, s. 1816-1825
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal dentate gyrus (DG) is an area of active proliferation and neurogenesis within the adult brain. The molecular events controlling adult cell genesis in the hippocampus essentially remain unknown. It has been reported previously that adult male and female rats from the strains Sprague Dawley (SD) and spontaneously hypertensive (SHR) have a marked difference in proliferation rates of cells in the hippocampal DG. To exploit this natural variability and identify potential regulators of cell genesis in the hippocampus, hippocampal gene expression from male SHR as well as male and female SD rats was analyzed using a cDNA array strategy. Hippocampal expression of the gene-encoding glucose-dependent insulinotropic polypeptide (GIP) varied strongly in parallel with cell-proliferation rates in the adult rat DG. Moreover, robust GIP immunoreactivity could be detected in the DG. The GIP receptor is expressed by cultured adult hippocampal progenitors and throughout the granule cell layer of the DG, including progenitor cells. Thus, these cells have the ability to respond to GIP. Indeed, exogenously delivered GIP induced proliferation of adult-derived hippocampal progenitorsin vivoas well asin vitro, and adult GIP receptor knock-out mice exhibit a significantly lower number of newborn cells in the hippocampal DG compared with wild-type mice. This investigation demonstrates the presence of GIP in the brain for the first time and provides evidence for a regulatory function for GIP in progenitor cell proliferation.
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| 3. |
- Brederlau, Anke, 1968, et al.
(författare)
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The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult hippocampal progenitor cell culture.
- 2004
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Ingår i: Molecular biology of the cell. - 1059-1524. ; 15:8, s. 3863-75
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Tidskriftsartikel (refereegranskat)abstract
- Bone morphogenetic proteins (BMPs) act as growth regulators and inducers of differentiation. They transduce their signal via three different type I receptors, termed activin receptor-like kinase 2 (Alk2), Alk3, or bone morphogenetic protein receptor Ia (BMPRIa) and Alk6 or BMPRIb. Little is known about functional differences between the three type I receptors. Here, we have investigated consequences of constitutively active (ca) and dominant negative (dn) type I receptor overexpression in adult-derived hippocampal progenitor cells (AHPs). The dn receptors have a nonfunctional intracellular but functional extracellular domain. They thus trap BMPs that are endogenously produced by AHPs. We found that effects obtained by overexpression of dnAlk2 and dnAlk6 were similar, suggesting similar ligand binding patterns for these receptors. Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced, whereas the number of oligodendrocytes increased. No effect on neuronal differentiation was seen. Whereas the expression of Alk2 and Alk3 mRNA remained unchanged, the Alk6 mRNA was induced after impaired BMP signaling. After dnAlk3 overexpression, cell survival and astroglial differentiation increased in parallel to augmented Alk6 receptor signaling. We conclude that endogenous BMPs mediate cell survival, astroglial differentiation and the suppression of oligodendrocytic cell fate mainly via the Alk6 receptor in AHP culture.
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- Larsson, Alice, et al.
(författare)
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Do patients with large vessel occlusion ischemic stroke harboring prestroke disability benefit from thrombectomy?
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 2667-2674
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Evidence of endovascular treatment (EVT) for acute large vessel occlusion (LVO) ischemic stroke in patients harboring substantial prestroke disability is lacking due to their exclusion from randomized trials. Here, we used routine care observational data to compare outcomes in patients with and without prestroke disability receiving EVT for LVO ischemic stroke. Methods: Consecutive patients undergoing EVT for acute LVO ischemic stroke at the Sahlgrenska University Hospital from January 1st, 2015 to March 31st, 2018 were registered in the Sahlgrenska Stroke Recanalization Registry. Pre- and poststroke functional levels were assessed by the modified Rankin Scale (mRS). Outcomes were recanalization rate (mTICI = 2b/3), symptomatic intracranial hemorrhage [sICH], complications during hospital stay, and return to prestroke functional level and mortality at 3 months. Results: Among 591 patients, 90 had prestroke disability (mRS ≥ 3). The latter group were older, more often female, had more comorbidities and higher NIHSS scores before intervention compared to patients without prestroke disability. Recanalization rates (80.0% vs 85.0%, p = 0.211), sICH (2.2% vs 6.3% p = 0.086) and the proportion of patients returning to prestroke functional level (22.7% vs 14.8% p = 0.062) did not significantly differ between those with and without prestroke disability. Patients with prestroke disability had higher complication rates during hospital stay (55.2% vs 40.1% p < 0.01) and mortality at 3 months (48.9% vs 24.3% p < 0.001). Conclusion: One of five with prestroke disability treated with thrombectomy for a LVO ischemic stroke returned to their prestroke functional level. However, compared to patients without prestroke disability, mortality at 3 months was higher. © 2020, The Author(s).
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