title: Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.
abstract: Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Cameco MS Neuroscience Research Center, Saskatoon City Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: Shari E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Cameco MS Neuroscience Research Center, Saskatoon City Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Figley
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Cameco MS Neuroscience Research Center, Saskatoon City Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schreyer
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Cameco MS Neuroscience Research Center, Saskatoon City Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: Phyllis G
authors.initials: PG
authors.lastname: Paterson
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D009457:Neuroglia / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism; D011502:Protein-Energy Malnutrition / Q000209:etiology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein