The overarching aim of the thesis research was to investigate mechanisms altered by protein-energy malnutrition (PEM), a common stroke co-morbidity factor that could affect the extent of brain damage and recovery following stroke. To model stroke, the rat 2-vessel occlusion model of global brain ischemia was employed. To characterize the effects of PEM, three states of malnutrition were assessed: PEM co-existing with brain ischemia (Study 1), effects of PEM independent of brain ischemia (Study 2), and PEM developing after brain ischemia (Study 3). The first hypothesis tested was co-existing PEM triggers an exacerbated glial response to global brain ischemia. The failure to achieve a consistent model of global ischemia prevented us from drawing conclusions on whether co-existing PEM exacerbates reactive gliosis. Nonetheless, this study demonstrated that mean temperature and temperature fluctuation are increased within the first 24hr of exposure to a low protein diet. The second hypothesis tested was PEM causes sustained changes in core temperature that are associated with an inflammatory response. Exposure to a low protein diet caused an immediate small and transient increase in mean temperature and a larger sustained increase in temperature amplitude. As malnutrition evolved, mean temperature declined. PEM stimulated an acute-phase response, characterized by an increase in the positive acute-phase protein, alpha-2-macroglobulin (A2M), and a decrease in the negative acute-phase protein, albumin. This response appeared to be aberrant, since the positive acute-phase protein, alpha-1-acid glycoprotein (AGP), was decreased with PEM. The final hypothesis tested was PEM developing after global brain ischemia exacerbates systemic and hippocampal inflammation, which is associated with diminished neuroplasticity. The effects of PEM on the acute-phase response are persistent following brain ischemia, as demonstrated by decreased serum albumin and increased serum A2M. A decrease in the positive acute-phase protein, haptoglobin, strengthened the evidence that PEM triggers an atypical reaction. The strong glial response elicited by global ischemia was unaltered by PEM. However, PEM influenced hippocampal neuroplasticity mechanisms, as GAP-43 and synaptophysin were significantly lower at d21. In summary, it has been demonstrated that PEM affects core temperature, the systemic acute-phase reaction and the neuroplasticity response to global brain ischemia.

Ischemic brain injury causes neurodegeneration. In this study, the mechanism of neurodegeneration was investigated by examining the role of sterol regulatory element binding protein-1 (SREBP-1), CCAAT enhancer binding protein&amp / #946 / (C/EBP&amp / #946 / ), glutathione (GSH), malondialdehyde (MDA), glutathione-S-transferase (GST), and superoxide dismutase (SOD). Carotid artery occlusion (CAO) plus hypotension was produced for 10 minutes. Control groups were sham operated. Animals were sacrificed after 24 hours, 1 week, 2 and 4 weeks of reperfusion periods. The expression of C/EBP&amp / #946 / and SREBP-1 in rat brain cortex and cerebellum were examined by western blotting. C/EBP&amp / #946 / expressions significantly increased in both cytosolic (1.19, 1.58 fold) and nuclear (1.73, 1.81 fold) extracts of brain cortex at 24 hours and 1 week CAO groups, respectively. In cerebellum, C/EBP&amp / #946 / expression significantly increased in 1 week, cytosolic (1.63 fold), and nuclear (1.35 fold) extracts. SREBP-1 expression increased significantly in both cytosolic (2.07 fold) and nuclear (1.41 fold) extracts of brain cortex in 1 week. SREBP-1 expression significantly increased in cytosolic (2.15 fold) and nuclear (1.79 fold) extracts of cerebellum in 1 week. There were no significant alterations in SREBP-1 C/EBP&amp / #946 / expressions for 2 and 4 weeks in both cytosolic and nuclear extracts of brain cortex and cerebellum. There were insignificant changes in GSH and GST levels in cortex. However, MDA and SOD levels significantly increased by 43.0 % and 47.3 %, respectively, in 24 hours. Our findings indicate that increase in SREBP-1 and C/EBP&amp / #946 / expressions may be related to oxidative stress during ischemic neurodegenerative processes.