Ischaemic stroke is a major cause of mortality and chronic disability for which there is no effective treatment. The subventricular zone (SVZ) is an adult neurogenic niche which mediates limited endogenous repair following stroke. To harness this phenomenon for therapy, it is important to understand how the SVZ niche is altered in stroke, and the processes that recruit neural precursors to the site of injury, which becomes a de facto neurogenic niche. Galectin-3 (Gal-3) is a β-galactoside binding protein involved in cellular adhesion, inflammation and tumour metastasis. Gal-3 is specifically expressed in the SVZ and maintains neuroblast migration to the olfactory bulb, although its role in post-stroke neurogenesis is not well-understood. Therefore, this project aimed to (1) characterise the cytoarchitecture of the SVZ in response to stroke, and (2) examine the role of Gal-3 in stroke outcome and tissue remodelling, and test the hypothesis that Gal-3 is required for neuroblast ectopic migration into the ischaemic striatum. Using the intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice, and whole mounts of the lateral ventricular wall, significant SVZ reactive astrocytosis and increased vascular branching were observed, thereby disrupting the neuroblast migratory scaffold. Stroke increased SVZ cell proliferation without increase in cell death. Post-stroke ependymal cells were enlarged and non-proliferative, and assumed a reactive astroglial phenotype, expressing de novo high levels of glial fibrillary acidic protein. This was associated with focal planar cell polarity misalignment, and turbulent and decreased rate of cerebrospinal fluid flow. These findings demonstrate significant changes in multiple SVZ cell types which are positioned to influence post-stroke neurogenesis and regulation of the neural stem cell niche Gal-3 was up-regulated in the ischaemic brain and ipsilateral SVZ. To elucidate the role of Gal-3 after stroke, MCAO was performed in wildtype and Gal-3 null (Gal-3^-/-) mice, and parameters of stroke outcome and post-stroke neurogenesis compared. The deletion of Gal-3 did not affect infarct volumes or neurological outcomes, although neuroblast migration into the ischaemic striatum was increased in Gal-3^-/- brains. Gal-3^-/- mice failed to mount an angiogenic response in the ischaemic striatum, and this was associated with lower levels of vascular endothelial growth factor (VEGF) and increased anti-angiogenic protein levels. Loss of Gal-3 further disrupted the pro-proliferative neural-vascular interaction at the basement membrane. The current data indicate that Gal-3 is a pleiotropic molecule which has distinct roles in both the SVZ and the post-stroke striatum as niches of adult neurogenesis.

Uppsatsen är en komparativ studie, där James D. G. Dunns och Thomas R. Schreiners tolkningar av vad som enligt Paulus gör att en människa räknas som rättfärdig samt varför Kristus dog utifrån Gal 2:15-21, 3:10 jämförs och värderas. Viktiga begrepp för tolkningen av dessa verser är rättfärdighet, δικαιοσύνη och laggärnigar, ἔργων νόμου. Dunn anser att rättfärdighet enligt Paulus nås genom att vara i Kristus, ἐν Χριστῷ vilket leder till en förändring av människans väsen till Kristuslikhet. Schreiner tolkar däremot rättfärdighet och rättfärdiggörelse som främst juridiskt, där det centrala är att tillräknas rättfärdighet från Kristus genom hans ställföreträdande syndaoffer. Utifrån de argument av Dunn och Schreiner som jag tar upp i analysen av Gal 2:15-21, 3:10 anser jag att Dunns tolkning av vad som leder till rättfärdighet enligt Paulus är mest rimlig. Om varför Kristus dog anser Dunn att det främst var för att göra förbundet med Gud tillgängligt för hedningarna, medan Schreiner anser att det främst var för att sona för människornas synder. Även på denna punkt anser jag att Dunns argument för sin ståndpunkt är mest rimliga.

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