Accumulating biochemical and morphological evidence suggests that apoptosis contributes to neuronal cell death following cerebral ischemia. Recent research which has examined changes in expression of proapoptotic proteins has further strengthened the important role of apoptosis in ischemic cell death. In this thesis I first addressed the role of apoptosis in ischemic death by examining p53, which is itself a complex multifunctional tumor suppresser gene, following transient focal ischemia. Of particular note were the alterations of the anti-apoptosic gene, naip, that were observed under stress conditions. The anatomical distribution of naip expression and neuronal survival following middle cerebral artery occlusion (MCA-o) were closely examined. In experiment I, SHR rats were subjected to 90 minute MCA-o followed by 22.5 hr reperfusion (RP) and compared with sham operated controls. In experiment II, sections obtained from fresh frozen or fixed brain tissue of long-Evans hooded rats (n = 3--4) that had been subjected to hippocampal kindling were used for ISHH or immunohistochemistry for naip expression. Neuronal protection against cerebral ischemia by hippocampal kindling was assessed in experiment III. Hippocampal kindled animals were also used to study the time course of naip expression in the frontoparietal cortex, which is mainly supplied by MCA. Both p53 mRNA and protein were elevated in the ischemic penumbra in experiment I. The induction of p53 peaked within 8--12 hr then returned to basal levels within 24 hr after RP. The short duration of p53 induction in ischemic penumbra may suggest that p53 activate downstream genes responsible for growth arrest, DNA repair or/and apoptosis. Experiment II demonstrated a significant elevation in naip mRNA and proteins in piriform cortex and hippocampus, where neuronal populations known to be protected by kindling. The duration of the elevation lasted up to three weeks. In contrast, naip mRNA and protein remained at baseline levels in regions that are not protected, such as endopiriform cortex and medial thalamus. We also demonstrated that hippocampal kindling attenuated cortical infarct induced by MCA-o to 57.7 +/- 4.6mm3 as compared to 156.5 +/- 12.6mm3 in controls. This neuroprotection was associated with a two to three fold elevation of naip expression in the corresponding areas by kindling treatment. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/6270 |
| Date | January 2002 |
| Creators | Huang, Zhigao. |
| Contributors | Staines, W., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 191 p. |
Page generated in 0.0024 seconds