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      Effects of protein-energy malnutrition on the inflammatory response to global brain ischemia

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      SMITH-DISSERTATION.pdf (3.131Mb)
      Date
      2015-10-20
      Author
      Smith, Shari
      Type
      Thesis
      Degree Level
      Doctoral
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      Abstract
      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.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Pharmacy and Nutrition
      Program
      Nutrition
      Supervisor
      Paterson, Phyllis G.
      Committee
      Nazarali, Adil; Bandy, Brian; Singh, Baljit; Colbourne, Fred; Tuor, Ursula
      Copyright Date
      June 2013
      URI
      http://hdl.handle.net/10388/ETD-2013-06-1076
      Subject
      protein-energy malnutrition
      inflammation
      global brain ischemia
      temperature
      acute-phase response
      neuroplasticity
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