An examination of the temporal and spatial evolution of a small permanent focal ischemic lesion
| dc.contributor.committeeMember | Obenaus, André | en_US |
| dc.creator | Bartnik, Brenda Lynn | en_US |
| dc.date.accessioned | 2008-07-28T13:22:25Z | en_US |
| dc.date.accessioned | 2013-01-04T04:48:48Z | |
| dc.date.available | 2009-08-18T08:00:00Z | en_US |
| dc.date.available | 2013-01-04T04:48:48Z | |
| dc.date.created | 2003 | en_US |
| dc.date.issued | 2003 | en_US |
| dc.date.submitted | 2003 | en_US |
| dc.description.abstract | The research reported here was designed to validate our hypothesis that noninvasive imaging could delineate the evolution of a small ischemic infarct. Furthermore, the alterations observed by MR were correlated to histological and inflammatory markers. Finally, intervention with a calcium buffering agent was hypothesized to prevent many of these changes. The first part of this study investigated the development of a small focal cortical lesion produced as a result of a cortical devascularization injury. Diffusion-weighted images (DWI) were collected before injury and at 12, 24, 48 hours and 3, 5, 7 and 14 days after injury and apparent diffusion coefficient (ADC) maps were calculated from the DW images to quantify lesion development. As a second measure of injury, tissue morphology was analyzed using cresyl violet histochemistry. Results indicated a significant reduction in ADC values within the lesion cortex that first appeared at 12 hours after injury and then recovered to control levels by 14 days. ADC changes were also observed in the contralateral cortex. This type of injury also resulted in the progressive but relatively slow formation of a pannecrotic infarct. Both astrocyte and microglia activation occurred early and were present in both hemispheres, however inflammatory cell infiltration was delayed until 48 hours after the injury. Many of these inflammatory cells were tumor necrosis factor a (TNF-a) and interferon y (IFN-y) immunoreactive. Overall, the quantitative and histological measures of this lesion were consistent with those observed in ischemic injury. Moreover, we found DWI to be a sensitive measure of damage associated with a cortical devascularization injury. The second part of this study used 2-aminophenol-N, N, O-triacetic acid acetoxymethyl ester (APTRA-AM) to determine the effectiveness of a calcium buffer in providing neuroprotection after a cortical devascularization injury. Animals were given two intravenous injections of either saline, DMSO, or APTRA-AM at 1 and 12 hours after injury. Animals were then imaged using a multiple b-value DWI sequence prior to injury and then at 12, 24,48 hours, 3 and 7 days after injury. After 7 days the animals were sacrificed and correlative histological and immunocytochemical studies were done. Our results indicate that saline injection after injury resulted in a decrease in the ADC of the lesion cortex within the first 12 hours of injury, which then slowly returned to prescan levels. In contrast, the injection of either DMSO or APTRA-AM after injury resulted in no significant changes in the ADC within the lesion area. Histologically, both saline and DMSO injected animals had pan-necrotic infarcts with concomitant glial activation and inflammatory cell infiltration. APTRA-AM treated animals showed an 86% reduction in lesion area and no evidence of inflammatory cell infiltration. The results presented here clearly demonstrate the effectiveness of APTRA-AM in preventing neuronal cell death and the accompanying inflammatory response when administered post-injury, suggesting that this molecule may be an excellent candidate for future clinical neuroprotection studies. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/etd-07282008-132225 | en_US |
| dc.language.iso | en_US | en_US |
| dc.title | An examination of the temporal and spatial evolution of a small permanent focal ischemic lesion | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Anatomy and Cell Biology | en_US |
| thesis.degree.discipline | Anatomy and Cell Biology | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) | en_US |