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Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation

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Abstract

Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke. Protein-energy status was assessed by a combination of body weight, food intake, serum acute phase proteins and corticosterone, and liver lipid content. Deficits in motor function were evaluated in the horizontal ladder walking and cylinder tasks at 3 days after stroke. The glial response and brain elemental signature were investigated by immunohistochemistry and micro-X-ray fluorescence imaging, respectively. The LP-fed rats reduced food intake, resulting in PEM. Pre-existing PEM augmented stroke-induced abnormalities in forelimb placement accuracy on the ladder; LP-St rats made more errors (29 ± 8%) than the NP-St rats (15 ± 3%; P < 0.05). This was accompanied by attenuated astrogliosis in the peri-infarct area by 18% and reduced microglia activation by up to 41 and 21% in the peri-infarct area and the infarct rim, respectively (P < 0.05). The LP diet altered the cortical Zn, Ca, and Cl signatures (P < 0.05). Our data suggest that proactive treatment of pre-existing PEM could be essential for optimal post-stroke recovery.

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Acknowledgements

The authors thank Sonia Cyrenne, Angela Cooper, and Megan Morgan for technical assistance and Samuel M. Webb and Courtney Roach for experimental station setup at Stanford Synchrotron Radiation Lightsource (SSRL) and providing thoughtful comments on the data set.

Sources of Funding

This study was funded by the Canadian Institutes of Health Research (CIHR)/Heart and Stroke Foundation of Canada (HSF) Grant No. 99472 (P.G.P. and H.N.); CIHR Operating Grant No. 111124 (P.G.P.); and HSF Grant-In-Aid (P.G.P).

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Authors and Affiliations

  1. College of Pharmacy and Nutrition, University of Saskatchewan, D Wing Health Sciences, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada

    Mariam Alaverdashvili, Sally Caine, Xue Li & Phyllis G. Paterson

  2. Department of Geological Sciences, University of Saskatchewan, Saskatoon, Canada

    Mark J. Hackett

  3. Department of Physics and Engineering Physics, University of Saskatchewan, Saskatoon, Canada

    Michael P. Bradley

  4. Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada

    Helen Nichol

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  1. Mariam Alaverdashvili
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Correspondence to Mariam Alaverdashvili or Phyllis G. Paterson.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.

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Alaverdashvili, M., Caine, S., Li, X. et al. Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation. Transl. Stroke Res. 9, 622–630 (2018). https://doi.org/10.1007/s12975-018-0613-3

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