Dietary Energy Restriction Ameliorates Cognitive Impairment in a Mouse Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young people. It was previously reported that dietary restriction, by either intermittent fasting (IF) or daily caloric restriction (CR), could protect neurons against dysfunction and degeneration in animal models of stroke and Parkinson’s disease. Recently, several studies have shown that the protein Sirtuin 1 (SIRT1) plays a significant role in the induced neuroprotection following dietary restriction. In the present study, we found a significant reduction of SIRT1 levels in the cortex and hippocampus in a mouse model of mild weight-drop closed head TBI. This reduction was prevented in mice maintained on IF (alternate day fasting) and CR initiated after the head trauma. Hippocampus-dependent learning and memory (measured using a novel object recognition test) was impaired 30 days post-injury in mice fed ad libitum, but not in mice in the IF and CR groups. These results suggest a clinical potential for IF and/or CR as an intervention to reduce brain damage and improve functional outcome in TBI patients.

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Acknowledgments

This research was supported in part by the Ari and Regine Aprijaskis Fund, at Tel-Aviv University and by the Intramural Research Program of the National Institute on Aging, NIH.

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Correspondence to V. Rubovitch.

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All applicable international, national, and/or, institutional guidelines for the care and use of animals were followed. If applicable (where such a committee exists), all procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Rubovitch, V., Pharayra, A., Har-Even, M. et al. Dietary Energy Restriction Ameliorates Cognitive Impairment in a Mouse Model of Traumatic Brain Injury. J Mol Neurosci 67, 613–621 (2019). https://doi.org/10.1007/s12031-019-01271-6

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Keywords

  • Traumatic brain injury
  • Cognitive deficits
  • Axonal regeneration
  • Intermittent fasting
  • Caloric restriction