Hypocaloric Diet Initiated Post-Ischemia Provides Long-Term Neuroprotection and Promotes Peri-Infarct Brain Remodeling b
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Hypocaloric Diet Initiated Post-Ischemia Provides Long-Term Neuroprotection and Promotes Peri-Infarct Brain Remodeling by Regulating Metabolic and Survival-Promoting Proteins Tayana Silva de Carvalho 1 & Eduardo H. Sanchez-Mendoza 1 & Adriana R. Schultz Moreira 1 & Luiza M. Nascentes Melo 1 & Chen Wang 1 & Maryam Sardari 1 & Nina Hagemann 1 & Thorsten R. Doeppner 2 & Christoph Kleinschnitz 1 & Dirk M. Hermann 1 Received: 17 June 2020 / Accepted: 9 November 2020 # The Author(s) 2020
Abstract Calorie restriction confers post-ischemic neuroprotection, when administered in a defined time window before ischemic stroke. How a hypocaloric diet influences stroke recovery when initiated after stroke has not been investigated. Male C57BL6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Immediately post-ischemia, mice were randomized to two groups receiving moderately hypocaloric (2286 kcal/kg food) or normocaloric (3518 kcal/kg) diets ad libitum. Animals were sacrificed at 3 or 56 days post-ischemia (dpi). Besides increased low density lipoprotein at 3 days and reduced alanine aminotransferase and increased urea at 56 days, no alterations of plasma markers were found in ischemic mice on hypocaloric diet. Body weight mildly decreased over 56 dpi by 7.4%. Hypocaloric diet reduced infarct volume in the acute stroke phase at 3 dpi and decreased brain atrophy, increased neuronal survival and brain capillary density in peri-infarct striatum and reduced motor coordination impairment in tight rope tests in the post-acute stroke phase over up to 56 dpi. The abundance of brain-derived neurotrophic factor, the NAD-dependent deacetylase and longevity protein sirtuin-1, the anti-oxidant glutathione peroxidase-3, and the ammonium detoxifier glutamine synthetase in the peri-infarct brain tissue was increased by hypocaloric diet. This study shows that a moderately hypocaloric diet that is initiated after stroke confers long-term neuroprotection and promotes peri-infarct brain remodeling. Keywords Calorie restriction . Ischemic stroke . Neurological recovery . Neuroprotection . Sirtuin-1
Introduction Caloric restriction extends lifespan, as previously shown in a large number of species that include yeast, nematodes, fruitflies, mice, and non-human primates [1–3]. In humans, the observations from animals recently prompted the randomized controlled Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy (CALERIE) trial, in which non-obese adults were randomized to normocaloric diet or a targeted 25% caloric restriction [4]. In the CALERIE trial, caloric restriction induced a reduction of energy expenditure * Dirk M. Hermann [email protected] 1
Department of Neurology, University Hospital Essen, Hufelandstraße 55, D-45122 Essen, Germany
2
Department of Neurology, University Medicine Göttingen, Göttingen, Germany
by ~10%, as revealed by the doubly labeled water method, and a reduction of lipid peroxidation, as evaluated by urinary F2-isoprostane measurement [4]. These data demon
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