Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

Ji, Liang; Nazarali, Adil J.; Paterson, Phyllis G.

doi:10.1016/j.jnutbio.2007.09.011

Cited by 17 publications

(10 citation statements)

References 56 publications

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“…The nonsteroidal GW3965, a LXR full agonist on both LXRα and LXRβ, (Collins et al, 2002) can cross the blood-brain barrier and exert specific actions on LXR receptors. In this study we therefore investigated whether LXR agonist can protect the brain through reducing NF-κB, activated after global ischemic insult (Ji et al, 2008;Rehni et al, 2009;Webster et al, 2009). We have found that LXR agonist has no effect on the phosphorylated IκBα, the major inhibitor of NF-κB (Zhang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-κB

et al. 2010

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Recent studies have found that liver X receptors (LXRs) agonists decrease inflammation and possess neuroprotective properties. The aim of this study was to examine the mechanisms of liver X receptor agonist GW3965 on brain injury following global cerebral ischemia in the rat. The 48 male SD rats were randomly partitioned into three groups: sham, global ischemia (4-vessel occlusion for 15 minutes; 4VO) treated with vehicle and global ischemia treated with GW3965 (20mg/kg, via i.p at 10 minutes after reperfusion). The functional outcome was determined by neurological evaluation at 24 hours post ischemia and by testing rats in T maze at 3 and 7 days after reperfusion. The rats' daily body weight, incidence of seizures and 72 hours mortality were also determined. After Nissl staining and TUNEL in coronal brain sections, the numbers of intact and damaged cells were counted in the CA1 sector of the hippocampus. The expression of phosphorylated inhibitor of κB (p-IκBα), Nuclear Factor-κB (NF-κB) subunit p65, and cyclo-oxygenase-2 (COX-2) were analyzed with Western blot at 12 hours after reperfusion. GW3965 tended to reduce 72 hours mortality and the incidence of post-ischemic seizures. GW3965-treated rats showed an improved neuronal survivability in CA1 and a significant increase in the percentage of spontaneous alternations detected in T-maze on day 7 after ischemia. GW3965-induced neuroprotection was associated with a significant reduction in nuclear translocation of NF-kB p65 subunit and a decrease in the hippocampal expression of NF-kB target gene, COX-2. LXR receptor agonist protects against neuronal damage following global cerebral ischemia. The mechanism of neuroprotection may include blockade of NF-κB activation and the subsequent suppression of COX-2 in the post ischemic brain.

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Section: Discussionmentioning

confidence: 99%

Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-κB

et al. 2010

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“…Chronic malnutrition has been reported to impair the ability to maintain thermoregulatory homeostasis [16][17][18], especially when animals are confronted with thermoregulatory challenges [17]. Therefore, an altered thermoregulatory response induced by PEM could explain some of the changes in the neuronal and glial response following global ischemia previously reported by our laboratory [10,11].…”

Section: Introductionmentioning

confidence: 75%

“…Clinical evidence, with noted methodological limitations, has demonstrated a correlation between PEM and increased morbidity and mortality following stroke [3][4][5]9]. A cause-and-effect relationship has been identified with the use of a rodent model of global brain ischemia demonstrating that PEM affects outcome on both a cellular and functional level [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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

Smith¹,

Prosser-Loose²,

Colbourne³

et al. 2011

CNR

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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.

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“…While clinical studies have focused on the relationship between nutritional status and infection rates, length of hospital stay [8], and muscle strength [11], we identified direct effects on the ischemic brain. In rodent models of global brain ischemia mimicking the clinical scenario of PEM pre-existing at the time of ischemia and continuing untreated, PEM appeared to lower the set-point for the inflammatory response in the vulnerable hippocampal CA1 subregion [10], [12]. This was evident as an increase in activation of the predominant pro-inflammatory transcription factor, nuclear factor kappa B [12], and, in a subset of malnourished rodents, an augmented glial response to global brain ischemia [10].…”

Section: Introductionmentioning

confidence: 99%

“…In rodent models of global brain ischemia mimicking the clinical scenario of PEM pre-existing at the time of ischemia and continuing untreated, PEM appeared to lower the set-point for the inflammatory response in the vulnerable hippocampal CA1 subregion [10], [12]. This was evident as an increase in activation of the predominant pro-inflammatory transcription factor, nuclear factor kappa B [12], and, in a subset of malnourished rodents, an augmented glial response to global brain ischemia [10]. While pre-existing PEM did not exacerbate neuronal death, neuroplasticity-related proteins were altered [10], [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

Cited by 17 publications

References 56 publications

Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-κB

Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-κB

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

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

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