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- Mostajeran, M., et al.
(författare)
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Acute mitogen-activated protein kinase 1/2 inhibition improves functional recovery and vascular changes after ischaemic stroke in rat-monitored by 9.4 T magnetic resonance imaging
- 2018
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 223:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim was to evaluate the beneficial effect of early mitogen-activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non-invasively for 2 weeks. Method: Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion. Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to evaluate cerebral perfusion at day 14. Immunohistochemistry evaluation of Ki67 was performed 14 days post-stroke. Results: U0126 improved long-term behavioural outcome and significantly reduced infarct size. In addition, cerebral perfusion in U0126-treated animals was improved compared to the vehicle group. Immunohistochemistry showed a significant increase in Ki67+ cells in U0126-treated animals compared to the vehicle group. Conclusion: Early MEK1/2 inhibition improves long-term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.
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| 4. |
- Christiansen, Anders T., et al.
(författare)
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Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model
- 2018
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X. ; 96:8, s. 812-820
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo. Methods: Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries. Results: Intravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately 65% of potassium-induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5. Conclusion: In seeming contrast to previous in vitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal arteries. This constriction could explain the worsening in vivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.
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| 5. |
- Hajiesmaeili, Mahboobeh, et al.
(författare)
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Sustaining high-value salmonid populations in regulated rivers : Insights from individual-based modelling of brown trout and Atlantic salmon
- 2024
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Ingår i: Global Ecology and Conservation. - : Elsevier. - 2351-9894. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- To combat climate change, societal pressure to develop fossil-free hydroelectricity is growing. There is a great need, however, for environmental assessment tools that can predict the effects of streamflow regulation on biodiversity in hydropower-regulated rivers. Ecological modelling lets practitioners: 1) set broad bounds on population-level responses of key species and 2) identify knowledge gaps and prioritize research needs. Individual-based models (IBMs) are powerful tools for assessing relative benefits of alternative management actions, and therefore help to develop more sustainable hydropower solutions. We applied the inSALMO 7.3-SD IBM for populations of brown trout (Salmo trutta) and Atlantic salmon (S. salar) in the lower Gullspång River, Sweden. We simulated the effects of various minimum hydropeaking flow releases (from 9 to 21 m3/s) on outmigration production. We found that the number of age-1 outmigrants of both species decreased with increasing minimum flow release of the hydropeaking scenarios. The number of age-2 trout outmigrants did not change considerably with increasing the minimum release, but decreased sharply at the highest flow. The most age-2 salmon outmigrants were produced by flow scenarios with minimum releases of 15 and 18 m3/s. The model predicts, therefore, varying species- and life stage-specific effects of flow regulation. Moreover, increased flow caused juveniles to stay in the river longer and outmigrate at larger size, which exposes them to simulated predation longer but could increase post-outmigration survival. By providing insights into mechanisms driving population dynamics, IBMs can help promote the sustainability of high-conservation-value fish species.
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| 6. |
- Stowell, Sean R, et al.
(författare)
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Galectins-1, -2 and -3 exhibit differential recognition of sialylated glycans and blood group antigens
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:15, s. 10109-10123
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Tidskriftsartikel (refereegranskat)abstract
- Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galss1-4Glc). To assess galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) on a glycan microarray containing hundreds of structurally diverse glycans. All three galectins exhibited unique glycan binding characteristics. Only Gal-1 and Gal-2 bound complex-type N-glycans and extended core 1 O-glycans with high affinity, while Gal-2 and Gal-3, but not Gal-1, bound A and B blood group antigens. Gal-2 failed to recognize any sialylated glycans regardless of linkage, whereas Gal-1 and Gal-3 bound a2-3, but not a2-6 sialylated glycans. All galectins showed higher binding to sulfated glycans relative to unsulfated ones. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (PL) sequences (Galss1-4GlcNAc)n when compared to N-acetyllactosamine (Galss1-4GlcNAc) in the microarray. However, only Gal-3 preferred PL when assessed by solution-based surface plasmon resonance. Removal of the terminal galactose residue in PL abrogated its recognition by Gal-1 and Gal-2 while having no substantial effect on Gal-3 recognition, demonstrating that Gal-3 recognizes internal N-acetyllactosamine units. These results provide novel insights into the functional constraints of glycan recognition by each galectin and underscore the basis for differences in biological activity.
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