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.

Malnutrition in Patients with Acute Stroke

“…Protein and energy malnutrition (PEM) on admission influences mechanisms of ischemic brain injury and impairs recovery [7]. PEM alters the expression of plasticity-associated genes that are associated with recovery mechanisms after global ischemia [7].…”

“…Protein and energy malnutrition (PEM) on admission influences mechanisms of ischemic brain injury and impairs recovery [7]. PEM alters the expression of plasticity-associated genes that are associated with recovery mechanisms after global ischemia [7]. PEM can also induce changes in hippocampal plasticity-associated proteins, suggesting that PEM may induce abnormalities in structure, function, and plasticity of hippocampal fibres [17].…”

“…Malnutrition is associated with poor outcome in these patients [6, 7]. We review the prevalence, consequences, and management of malnutrition in patients with stroke.…”

Protein-Energy Malnutrition Developing after Global Brain Ischemia Induces an Atypical Acute-Phase Response and Hinders Expression of GAP-43

“…Diets were modified from the American Institute of Nutrition-93G diet [31]; the diet composition was previously described in detail [24]. Rats of this age fed a 2% protein diet voluntarily reduce food consumption, thereby causing a decrease in both energy and protein intake [24], [32]. Body weight and food intake were recorded on the day of surgery (day 0) and post-surgical days 1 and 2.…”

Multiple Chronic Conditions Explain Ethnic Differences in Functional Outcome Among Patients With Ischemic Stroke

“…6,7 Congestive heart failure (CHF), diabetes, chronic kidney disease, malnutrition, and preexisting neurological diseases have been found to impact FO potentially through stroke-specific pathophysiological pathways, which may collectively deplete the overall cardiovascular reserve or impair the neuroplasticity that aids in poststroke recovery. [8][9][10][11][12] However, research on MCC and FO in diverse populations is lacking, and the role of MCC in the ethnic difference in FO is poorly understood.…”