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Neuronal injury from cardiac arrest: aging years in minutes

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Abstract

Cardiac arrest is a leading cause of death and permanent disability. Most victims succumb to the oxidative and inflammatory damage sustained during cardiac arrest/resuscitation, but even survivors typically battle long-term neurocognitive impairment. Although extensive research has delineated the complex mechanisms that culminate in neuronal damage and death, no effective treatments have been developed to interrupt these mechanisms. Of importance, many of these injury cascades are also active in the aging brain, where neurons and other cells are under persistent oxidative and inflammatory stress which eventually damages or kills the cells. In light of these similarities, it is reasonable to propose that the brain essentially ages the equivalent of several years within the few minutes taken to resuscitate a patient from cardiac arrest. Accordingly, cardiac arrest-resuscitation models may afford an opportunity to study the deleterious mechanisms underlying the aging process, on an accelerated time course. The aging and resuscitation fields both stand to gain pivotal insights from one another regarding the mechanisms of injury sustained during resuscitation from cardiac arrest and during aging. This synergism between the two fields could be harnessed to foster development of treatments to not only save lives but also to enhance the quality of life for the elderly.

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Abbreviations

AD:

Alzheimer’s disease

Bak:

Bcl-2 homologous antagonist killer

Bax:

Bcl-2-associated X protein

BBB:

Blood–brain barrier

Bcl-2:

B-cell lymphoma 2 family of proteins

BH4 :

Tetrahydrobiopterin

Casp-3:

Caspase-3

Casp-9:

Caspase-9

CoQ:

Coenzyme-Q

CPR:

Cardiopulmonary resuscitation

Cyt C:

Cytochrome C

eNOS:

Endothelial isoform of nitric oxide synthase

GSH:

Reduced form of glutathione

GSH/GSSG:

Concentration ratio of reduced to oxidized glutathione

iNOS:

Inducible isoform of nitric oxide synthase

mPTP:

Mitochondrial permeability transition pore

mtDNA:

Mitochondrial DNA

NFκB:

Nuclear factor-kappa B

NO:

Nitric oxide

O2 − :

Superoxide

ONOO− :

Peroxynitrite

OxS:

Oxidative stress

ROS/RNS:

Reactive oxygen and nitrogen species

SMAC:

Second mitochondria-derived activator of caspases

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

This work was supported by research grant R01 NS076975 from the U.S. National Institute of Neurological Disorders and Stroke and by research grant P01 AG22550 from the National Institute on Aging. BHC was supported by a pre-doctoral fellowship from the National Institute of Aging, Training in the Neurobiology of Aging, grant T31 AG020494. This work was conducted in partial fulfillment of the requirements for the Ph.D. degree for BHC.

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Authors and Affiliations

  1. Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA

    Brandon H. Cherry & Robert T. Mallet

  2. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA

    Nathalie Sumien

  3. Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA

    Brandon H. Cherry, Nathalie Sumien & Robert T. Mallet

  4. Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA

    Brandon H. Cherry & Robert T. Mallet

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  1. Brandon H. Cherry
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  2. Nathalie Sumien
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Correspondence to Brandon H. Cherry.

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Cherry, B.H., Sumien, N. & Mallet, R.T. Neuronal injury from cardiac arrest: aging years in minutes. AGE 36, 9680 (2014). https://doi.org/10.1007/s11357-014-9680-x

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