期刊
FRONTIERS IN NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.609670
关键词
cardiac arrest; caloric restriction; neurological recovery; cerebral ischemia; dietary restriction
资金
- NIH [R21EB024793, 5KL2TR0001416, UL1 TR001414]
- UC Irvine School of Medicine Committee on Research and Graduate Academic Programs
- UC Irvine School of Medicine
- UC Irvine Department of Neurology
- Roneet Carmell Memorial Endowment Fund
It has been shown that overnight caloric restriction improves survival and neurological recovery in acute ischemic brain injury models, by normalizing stress-induced hyperglycemia and affecting hormone production. These benefits appear unrelated to SIRT-1 and BDNF expression, with mechanisms still needing further clarification.
While interest toward caloric restriction (CR) in various models of brain injury has increased in recent decades, studies have predominantly focused on the benefits of chronic or intermittent CR. The effects of ultra-short, including overnight, CR on acute ischemic brain injury are not well studied. Here, we show that overnight caloric restriction (75% over 14 h) prior to asphyxial cardiac arrest and resuscitation (CA) improves survival and neurological recovery as measured by, behavioral testing on neurological deficit scores, faster recovery of quantitative electroencephalography (EEG) burst suppression ratio, and complete prevention of neurodegeneration in multiple regions of the brain. We also show that overnight CR normalizes stress-induced hyperglycemia, while significantly decreasing insulin and glucagon production and increasing corticosterone and ketone body production. The benefits seen with ultra-short CR appear independent of Sirtuin 1 (SIRT-1) and brain-derived neurotrophic factor (BDNF) expression, which have been strongly linked to neuroprotective benefits seen in chronic CR. Mechanisms underlying neuroprotective effects remain to be defined, and may reveal targets for providing protection pre-CA or therapeutic interventions post-CA. These findings are also of high importance to basic sciences research as we demonstrate that minor, often-overlooked alterations to pre-experimental dietary procedures can significantly affect results, and by extension, research homogeneity and reproducibility, especially in acute ischemic brain injury models.
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