title: Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.
abstract: Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p<0.05), none of these variables (nor hematocrit) correlated significantly with CA1 cell counts in the malnourished group exposed to 2-VO (p>0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Prosser-Loose
authors.forename: Shari E
authors.initials: SE
authors.lastname: Smith
authors.forename: Phyllis G
authors.initials: PG
authors.lastname: Paterson
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007022:Hypotension / Q000150:complications / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011488:Protein Deficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley