Protein-Energy Malnutrition Alters Thermoregulatory Homeostasis and the Response to Brain Ischemia

Abstract

Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p < 0.027). In the immediate post-surgical period, PEM decreased body temperature to a greater extent than that in well-nourished controls (p = 0.003). The increase in daily temperature fluctuation caused by PEM persisted throughout the 7 day post-surgical period (p < 0.001), and this interacted with the effects of global ischemia on days 8 (p = 0.018) and 11 (p = 0.021). The astrocytic and microglial responses induced at 7 days after global ischemia were not influenced by PEM, but this preliminary analysis needs to be confirmed with a more reliable global ischemia model. In conclusion, exposure to a low protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke victims with coexisting PEM.

Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray Fluorescence Imaging at the Sulfur K-Edge

“…31 Brain tissue was obtained from the rats 5 days after sham surgery or brain ischemia ( n = 5 for sham surgery and n = 5 for ischemia). All rats were housed with a 12 h light/12 h dark cycle with ad libitum access to chow and water.…”

Malnutrition in Patients with Acute Stroke

“…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]. Following global ischemia in experimental models, PEM intensifies the expression of trkB and GAP-43 protein in the hippocampus, indicating both an increased stress response and hyperexcitability in the hippocampal circuitry [17, 23]. …”

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

“…The decrease in the negative acute-phase protein, albumin, on day 2 after nutritional intervention (5 days following global ischemia) was sustained at day 21, at which time the rise in the class 2 positive acute-phase protein, A2M, also became significant. Our previous findings suggest that this reaction exists without a febrile response [24], [29]. The acute-phase response was selective, however, as the class 1 acute-phase protein, AGP, was unchanged, and haptoglobin was decreased after 2 days of exposure to the PEM regimen and barely detectable by day 21.…”

“…Following a 4–6 day acclimation period on CON diet, rats were randomly allocated to undergo either sham surgery (Sham) or transient forebrain ischemia via the 2-vessel occlusion (2-VO) model (ISC), as previously described [29] and modified from Smith et al . [30].…”