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Overnight caloric restriction prior to cardiac arrest and resuscitation leads to improved survival and neurological outcome in a rodent model

View ORCID ProfileMatine Azadian, Guilian Tian, Afsheen Bazrafkan, Niki Maki, Masih Rafi, Monica Desai, Ieeshiah Otarola, Shuhab Zaher, Ashar Khan, Yusuf Suri, Minwei Wang, Oswald Steward, Yama Akbari
doi: https://doi.org/10.1101/786871
Matine Azadian
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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  • ORCID record for Matine Azadian
Guilian Tian
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Afsheen Bazrafkan
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Niki Maki
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Masih Rafi
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Monica Desai
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Ieeshiah Otarola
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Shuhab Zaher
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Ashar Khan
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Yusuf Suri
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Minwei Wang
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
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Oswald Steward
2Reeve-Irvine Research Center, Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA, USA
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Yama Akbari
1Department of Neurology, School of Medicine, University of California, Irvine, CA, USA
3Beckman Laser Institute, University of California, Irvine, CA, USA
4Department of Neurological Surgery, School of Medicine, University of California, Irvine, CA, USA
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  • For correspondence: yakbari@gmail.com
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Abstract

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, however, 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, including 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. Further exploration into the precise mechanisms involved in ultra-short CR may have significant translational implications. These findings are also of 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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Posted September 30, 2019.
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Overnight caloric restriction prior to cardiac arrest and resuscitation leads to improved survival and neurological outcome in a rodent model
Matine Azadian, Guilian Tian, Afsheen Bazrafkan, Niki Maki, Masih Rafi, Monica Desai, Ieeshiah Otarola, Shuhab Zaher, Ashar Khan, Yusuf Suri, Minwei Wang, Oswald Steward, Yama Akbari
bioRxiv 786871; doi: https://doi.org/10.1101/786871
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Overnight caloric restriction prior to cardiac arrest and resuscitation leads to improved survival and neurological outcome in a rodent model
Matine Azadian, Guilian Tian, Afsheen Bazrafkan, Niki Maki, Masih Rafi, Monica Desai, Ieeshiah Otarola, Shuhab Zaher, Ashar Khan, Yusuf Suri, Minwei Wang, Oswald Steward, Yama Akbari
bioRxiv 786871; doi: https://doi.org/10.1101/786871

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