Overnight Caloric Restriction Prior to Cardiac Arrest and Resuscitation Leads to Improved Survival and Neurological Outcome in a Rodent Model

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 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.

A critical role for spike synchrony in determining steep 1/f slopes in the setting of bursting EEG patterns

“…Likewise, 1/f slope might also be used to differentiate or prognosticate coma status in parallel with existing burst suppression metrics, or even perhaps guide pharmacological interventions on coma. For example, the time to resumption of EEG bursting after cardiac arrest depends on cerebral perfusion [Crouzet et al, 2016, Azadian et al, 2021, Wilson et al, 2019], so 1/f slope analysis of this bursting state might constrain microcircuit models of how re-perfusion modulates neuronal dynamics. Thus, the present model of 1/f slope may be used to further understanding of how different anesthetics modulate the synchronization of neural circuits and subsequently alter consciousness.…”

Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome

“…The animal model of asphyxial cardiac arrest and resuscitation used in this study has been described previously [ 9 , 26 – 28 ] by our laboratory and is summarized in Fig. 1 .…”

“…Briefly, male Wistar rats (Charles River Laboratories) of 8 to 12 weeks of age weighing 300 to 400 g were handled daily for at least 1 week prior to any experimentation. The night prior to cardiac arrest experiments, rats were calorically restricted (75% restriction) with three food pellets, as is standard with our model [ 26 ]. The next morning, rats were endotracheally intubated and received femoral artery and vein cannulation to enable arterial blood pressure monitoring and venous drug delivery, respectively.…”

Intrinsic, widefield optical imaging of hemodynamics in rodent models of Alzheimer’s disease and neurological injury

“…This monitoring was performed during entry into cardiac arrest, CPR, and reperfusion in a setup mimicking an intensive care unit. 61 , 76 , 200 , 214 This setup provided high-speed ( ) SFDI mapping of chromophores, which enabled the requisite temporal resolution to monitor rapid hemodynamic changes and calculate cerebral pulsatility. SFDI revealed rapid cerebral changes in the hemoglobin concentrations and oxygenation during cardiac arrest and immediately post-CPR that were distinct from changes in the tissue during these same time periods [ Fig.…”