- Title
- Investigation of corticosterone impact on the sub-acute stage of recovery after photothrombotic stroke induction
- Creator
- Zalewska, Katarzyna
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Stroke is a detrimental, life- threatening condition which affects almost 15 million people worldwide. Currently the gold standard for the treatment of acute ischaemic stroke involves either the delivery of thrombolytic agents, such as alteplase (rtPa), or the direct removal of the clot utilising a mechanical retrieval device. Although success rates using these treatments have continued to rise, it is still the case that the ‘numbers needed to treat’ (NNT) statistics indicate that many patients do not derive significant benefit. As such, it estimated that >90% of patients that suffer from stroke will live with some degree of brain damage and associated functional impairment. The functional impairments that appear after stroke can be varied and are often multi-modal influencing motor function, mood, cognition and sensation. The rapid onset of these impairments combined with their severity mean that many patients experienced significant levels of stress, as result of changes in lifestyle and independence. While the stress that many patients experience is completely understandable it is also highly problematic, as the stress response, produces a number of signalling molecules that can directly interfere with the processes involved in brain repair. The primary objective of the current thesis was to explore how stress, and in particular key stress signalling molecules, could influence brain repair post-stroke. Specifically, I was interested in determining how many of the negative effects of stress on the recovery process could be emulated via the delivery of one of the main stress signalling molecules, known as corticosterone. Corticosterone is a steroid hormone released at high levels from the adrenal cortex during the stress response. The hormone itself is highly pleiotropic, however, is best recognised to stimulate the production of glucose, a critical resource for responding to the stressful event. I was motivated to specifically explore the effects of corticosterone on the cellular repair processes following stroke because I reasoned that if corticosterone was responsible for a large variety of effects seen using stress then it may be worthwhile trying to pharmacologically block this molecule after the stress process. To study how corticosterone delivery affects recovery after stroke I combined photothrombotic stroke model with a number of molecular biology techniques like the Western Blot (WB), Immunohistochemistry (IHC), various histological staining and ELISAs. Moreover, I used a battery of behavioural tasks to investigate functional recovery post- stroke. In short I considered the effects of corticosterone delivery of a variety of systems including white matter tracts, neurons, glia, and motor function. The results I obtained indicated that corticosterone only produced some of the effects on repair that are known to be induced by stress, indicating that efforts to block corticosterone release were unlikely to be a productive avenue to explore in future studies. I also spent a considerable block of time in my doctoral studies exploring an interesting technology, known as intrinsic optical signal imaging. In short this technique allows for visualisation of changes in haemoglobin within the brain. My goal here was to use this technique to examine cortical remodelling in the brain in animals exposed to the stress hormone corticosterone. While we successfully developed this technique a number of technical limitations prevented its continued use in all the experimental studies that I undertook. In conclusion, the work has made a number of significant and original contributions to the literature, and in particular developed and much more detailed and nuanced view of how one of the major stress signalling hormones influences the quality and extend of brain repair after stroke.
- Subject
- stress; stroke; immunohistochemistry; thesis by publication; corticosterone; white matter tracks; neurovascular unit; microglia; astrocytes; blood vessels; neurons; western blot
- Identifier
- http://hdl.handle.net/1959.13/1403610
- Identifier
- uon:35193
- Rights
- Copyright 2018 Katarzyna Zalewska
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 23 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 697 KB | Adobe Acrobat PDF | View Details Download |