Abstract
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.
Highlights
Protein-energy malnutrition (PEM) is commonly associated with stroke
We found that PEM developing after global brain ischemia inhibits the expression of axon terminal proteins that serve as markers for synaptic remodeling in the hippocampal CA3 mossy fibers
Introducing this regimen on the third post-ischemic day provided evidence that PEM could interfere with axonal sprouting elicited by brain ischemia
Summary
Protein-energy malnutrition (PEM) is commonly associated with stroke. Pre-existing PEM is present in 12–19% of patients admitted to hospital with a diagnosis of stroke [1,2,3]. 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]. Whereas glial cells activated by brain ischemia can secrete growth factors [15,16] that promote neuroplasticity, over-expression of pro-inflammatory cytokines and neuroinflammation can inhibit synaptic plasticity [17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
