Caloric restriction stabilizes body weight and accelerates behavioral recovery in aged rats after focal ischemia

Abstract

SummaryObesity and hyperinsulinemia are risk factors for stroke. We tested the hypothesis that caloric restriction, which reduces the incidence of age‐related obesity and metabolic syndrome, may represent an efficient and cost‐effective strategy for preventing stroke and its devastating consequences. To this end, we placed aged, obese Sprague‐Dawley aged rats on a calorie‐restricted diet for 8 weeks prior to the experimental infarction. Stroke in this animal model caused a progressive decrease in weight that reached a minimum at day 6 for the young rats, and at day 10 for the aged, ad libitum‐fed rats. However, in aged animals that were calorie‐restricted prior to stroke, body weight did not decrease after stroke, but we noted accelerated body weight gain shortly thereafter starting at day 5 poststroke. Moreover, calorie‐restricted aged animals showed improved behavioral recovery in tasks requiring complex sensorimotor skills, or in tasks requiring cutaneous sensitivity and sensorimotor integration or spatial memory. Likewise, calorie‐restricted aged rats showed significant poststroke increases in serum glucose, insulin, and IGF1 levels, as well as CR‐specific changes in the expression of gene transcripts involved in glycogen metabolism, IGF signaling, apoptosis, arteriogenesis, and hypoxia. In conclusion, our study shows that recovery from stroke is enhanced in aged rats by a dietary regimen that reduces body weight prior to infarct.

Neuroprotection Induced by Energy and Protein-Energy Undernutrition Is Phase-Dependent After Focal Cerebral Ischemia in Mice

“…Previous studies in animal models of focal cerebral ischemia found that undernutrition reduces brain injury [7-9, 16, 17], whereas other studies in models of focal or global ischemia showed that ischemic injury was unchanged by undernutrition [10][11][12][13]. A variety of studies in models of focal or global ischemia observed a significant reduction of stroke-induced neurological deficits [7][8][9][10][11], whereas other studies, again in focal or global ischemia, noted exacerbated or unchanged deficits [12][13][14][15]. Major differences in these studies relate to the type of undernutrition.…”

“…Major differences in these studies relate to the type of undernutrition. As such, undernutrition was induced by (a) reducing food access to 60 or 70% of the average amount of control animals for 4 weeks to 3 months [8,10,13,16], (b) reducing food protein content to 0 to 12% for 6 days to 4 weeks [9,12,14,15], or (c) intermittent fasting on alternate days or twice per week for one to several months [7,11,17]. While reducing the amount of food access similarly reduces protein and energy consumption, the reduction of protein content to 0-2% results in a reduction in the total amount of food ingested, since the animals refuse this chow [9,12,14,15].…”

“…The preceding regulation of metabolism-related genes (Sirt-1, Glut-1) indicates that tissue energy demands had been adjusted which enabled the tissue to survive ischemic injury. Ischemic tolerance can similarly be induced by intermittent fasting in young and aged rats [7,11,17], suggesting that this type of endogenous protection might Table 2 Undernutrition regulates metabolism-related, pro-oxidant, and anti-oxidant genes in the liver also be induced in elderly humans by repeated short-lasting food restriction episodes. Diet modification induces a series of physiological and biochemical responses that we did not examine in this study, such as changes in blood gases, as well as changes of plasma glucose and lipids that we evaluated prior to animal sacrifice but not at baseline.…”

“…Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12975-019-00700-3) contains supplementary material, which is available to authorized users. experimental studies showed that continuous or intermittent food restriction reduces post-ischemic neurological deficits [7][8][9][10][11], whereas other studies found exacerbated or unchanged neurological impairments [12][13][14][15]. Some studies showed that undernutrition reduced histological brain injury [7-9, 16, 17], whereas other studies observed no effect [10][11][12][13].…”

“…experimental studies showed that continuous or intermittent food restriction reduces post-ischemic neurological deficits [7][8][9][10][11], whereas other studies found exacerbated or unchanged neurological impairments [12][13][14][15]. Some studies showed that undernutrition reduced histological brain injury [7-9, 16, 17], whereas other studies observed no effect [10][11][12][13]. Some studies reported anti-inflammatory effects related to undernutrition, that is, reduced microglial activation [15] and decreased interleukin (IL)-1β, IL-6, or tumor necrosis factor-α (TNF-α) levels in the brain and blood [9,16,17].…”