title: Protein-energy malnutrition increases activation of the transcription factor, nuclear factor kappaB, in the gerbil hippocampus following global ischemia.
abstract: Protein-energy malnutrition (PEM) exacerbates functional impairment caused by brain ischemia. This is correlated with reactive gliosis, which suggests an increased inflammatory response. The objective of the current study was to investigate if PEM increases hippocampal activation of nuclear factor kappaB (NFkappaB), a transcription factor that amplifies the inflammatory response involved in ischemic brain injury. Mongolian gerbils (11-12 weeks old) were randomly assigned to control diet (12.5% protein) or protein-deficient diet (2%) for 4 weeks. The 2% protein group had a 15% decrease in voluntary food intake (P<.001; unpaired t test), resulting in PEM. Body weight after 4 weeks was 20% lower in the PEM group (P<.001). Gerbils were then exposed to sham surgery or global ischemia induced by 5-min bilateral common carotid artery occlusion. PEM independently increased hippocampal NFkappaB activation detected by electrophoretic mobility shift assay at 6 h after surgery (P=.014; 2-factor ANOVA). Ischemia did not significantly affect NFkappaB activation nor was there interaction between diet and ischemia. Serum glucose and cortisol concentrations at 6 h postischemia were unaltered by diet or ischemia. A second experiment using gerbils of the same age and feeding paradigm demonstrated that PEM also increases hippocampal NFkappaB activation in the absence of surgery. These findings suggest that PEM, which exists in 16% of elderly patients at admission for stroke, may worsen outcome by increasing activation of NFkappaB. Since PEM increased NFkappaB activation independent of ischemia or surgery, the data also have implications for the inflammatory response of the many individuals affected globally by PEM.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5C9.
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.forename: Adil J
authors.initials: AJ
authors.lastname: Nazarali
authors.forename: Phyllis G
authors.initials: PG
authors.lastname: Paterson
mesh_terms: D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D007511:Ischemia; D008297:Male; D008954:Models, Biological; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D011502:Protein-Energy Malnutrition / Q000378:metabolism*; D020521:Stroke
chemical_list: D001786:Blood Glucose; D016328:NF-kappa B; D006854:Hydrocortisone