|Title:||The neuropathology of age-related degenerations: Cause and protection assessed in rodent models|
|Publisher:||University of Sydney.|
Sydney Medical School.
Discipline of Physiology.
|Abstract:||Neurodegenerative diseases such as age-related dementia (ARD; Alzheimer’s disease) and Parkinson’s disease are a consequence of age-related pathological changes in the central nervous system (CNS). There is a growing body of evidence that ARD is a vascular dementia, caused by micro-haemorrhages from cerebral capillaries. Oxidative stress and mitochondrial dysfunction caused by haemorrhage are then thought to cause the features of the demented brain which Alzheimer described (senile plaques, neurofibrillary tangles and inflammation) and the cell death, synaptic loss and the formation of abnormal proteins described since. In this project, I have used rodent models to test the causal relationship between cerebral haemorrhage and the formation of plaques and neurofibrillary tangles, and to test the potential of two neuroprotectants, dietary saffron and photobiomodulation (with near infrared light), to mitigate neuropathological changes in rodent models of cerebral degenerations. Further, a detailed analysis is presented of the effect of haemorrhage on tissue flanking a haemorrhage site; the analysis suggests the upregulation of protective mechanisms in this flanking tissue. It is possible that the neuroprotectants, saffron and photobiomodulation act by upregulating these endogenous protective mechanisms. Overall, the results provide support for the microvascular hypothesis of age-related dementia, and provide evidence that preconditioning brain tissue can mitigate the pathology associated with dementia, and give insight into underlying mechanisms.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|PURUSHOTHUMAN Sivaraman - Final thesis.pdf||Final thesis||47.39 MB||Adobe PDF|
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