Brain nuclear DNA survives cardiac arrest and reperfusion

White, Blaine C.; DeGracia, Donald J.; Krause, Gary S.; Skjaerlund, John M.; O’Neil, Brian J.; Grossman, Lawrence I.

doi:10.1016/0891-5849(91)90006-o

Cited by 21 publications

(9 citation statements)

References 43 publications

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“…Despite the existence of several papers on DNA damage in cardiac disease (11–20), currently, very few papers have been published on genomic markers during and after OHCA (2, 21–24). White et al (21) tested DNA from the cerebral cortex of dogs during their reperfusion following resuscitation for cardiac arrest, but no significant damage was found.…”

Section: Discussionmentioning

confidence: 99%

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Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

Hazuková

Řezáčová

Köhlerová³

et al. 2017

Anatol J Cardiol

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Objective:This study aimed to investigate whether out-of-hospital cardiac arrest (OHCA) may induce severe DNA damage measured using comet assay in successfully resuscitated humans and to evaluate a short-term prognostic role.Methods:In this prospective, controlled, blinded study (1/2013–1/2014), 41 patients (age, 63±14 years) successfully resuscitated from non-traumatic OHCA and 10 healthy controls (age, 53±17 years) were enrolled. DNA damage [double-strand breaks (DSBs) and single-strand breaks (SSBs)] was measured using comet assay in peripheral lymphocytes sampled at admission. Clinical data were recorded (according to Utstein style). A good short-term prognosis was defined as survival for 30 days.Results:Among the patients, there were 71% (29/41) short-term survivors. After OHCA, DNA damage (DSBs and SSBs) was higher (11.0±7.6% and 0.79±2.41% in tail) among patients than among controls (1.96±1.63% and 0.02±0.03% in tail), and it was more apparent for DSBs (p<0.001 and p=0.085). There was no difference in the DNA damage between patients with cardiac and non-cardiac etiology, or between survivors and nonsurvivors. Among Utstein style parameters, ventricular fibrillation, asystole, and early electrical defibrillation influenced DSB; none of the factors influenced SSBs. Factors influencing survival were SSBs, ventricular fibrillation, length of cardiopulmonary resuscitation by professionals ≤15 min, cardiogenic shock, and postanoxic encephalopathy. In contrast to DSBs [area under the curve (AUC)=0.520], SSBs seem to have a potential in prognostication (AUC=0.639).Conclusion:This study for the first time demonstrates revelation of DNA damage using comet assay in patients successfully resuscitated from OHCA. Whether DNA damage measured using comet assay may be a prognostic marker remains unknown, although our data may encourage some suggestions.

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Section: Discussionmentioning

confidence: 99%

“…White et al (21) tested DNA from the cerebral cortex of dogs during their reperfusion following resuscitation for cardiac arrest, but no significant damage was found. However, a crucial limitation is that any study of DNA integrity in the cerebral cortex is inapplicable for clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

Hazuková

Řezáčová

Köhlerová³

et al. 2017

Anatol J Cardiol

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“…Twenty-four dogs were divided into four equal groups: (1) nonischemic controls, in which the tissue samples were taken without an ischemic insult; (2) 20-min cardiac arrest without resuscitation; (3) 20-min cardiac arrest followed by resuscitation and 2 h of postresuscitation intensive care; and (4) 8 h of postresuscitation intensive care. Methods for anesthesia, induction of cardiac arrest, resuscitation, monitoring of hemodynamic parameters and core temperature, postresuscitation care, and surgical access to the brain have all been previously described by White et al (1991).…”

Section: Animal Modelmentioning

confidence: 99%

“…Samples of parietal cortex weighing about 3 g were obtained, trimmed to remove most of the subcortical white matter, diced, and then homogenized in 25 ml of ice-cold DNA isolation solution within 60 s oftissue sampling (White et al,199 1). DNA was isolated both from the nuclear pellet (White et al, 1991) and from purified mitochondria; the distribution of mtDNA topological forms was examined in both DNA fractions but only the purified mtDNA was used to label gaps. The mitochondria were collected by centrifugation (20 rnin at 27,000 g, 4OC) of the postnuclear supernatant.…”

Section: Isolation Of Brain Dnamentioning

confidence: 99%

“…Such damage to mtDNA during reperfusion could adversely affect both subsequent synthesis of mitochondrial-coded proteins and the cells' ability to recover from the ischemic insult. We previously found no radical-mediated damage to brain nuclear DNA during 8 h of reperfusion following a 20min cardiac arrest (White et al, 1991). Because mitochondria lack nucleotide excision or recombination repair (Clayton et al, 1975;Niranjan et al, 1982), and a single nick of the supercoiled form is readily detected, evaluation of mtDNA offered an independent and possibly more sensitive test for radical-mediated DNA damage.…”

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Brain Mitochondrial DNA Is Not Damaged by Prolonged Cardiac Arrest or Reperfusion

White

Tribhuwan

Laan

et al. 1992

Journal of Neurochemistry

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Postischemic reperfusion is known to cause iron-mediated peroxidation of polyunsaturated fatty acids in membranes, including mitochondrial membranes, in the brain cortex. Consequently, we tested the hypothesis that this radical-mediated damage would extend to DNA. Mitochondrial DNA (mtDNA) was chosen because of its presence at a known site of free radical formation, its sensitivity and ease of assay, and its known lack of any repair systems. In model experiments we utilized endonuclease III or piperidine to amplify topological form conversions in mtDNA damaged by in vitro reactions with hydroxyl radical. We then applied the amplified detection assays to dog brain mtDNA isolated after 2 or 8 h of reperfusion following a 20-min cardiac arrest. We found that ischemia and reperfusion caused no topological form conversions in mtDNA. Similarly, nucleotide incorporation by a gap-filling reaction showed no sensitivity to digestion of the mtDNA by exonuclease III, an enzyme known to remove blocked 3' termini at the site of radical-generated nicks. Furthermore, the recovery of mtDNA was similar in all experimental groups, suggesting that putatively damaged forms had not been removed by rapid degradation. Thus, despite mitochondrial membrane damage, brain mtDNA does not accumulate oxygen radical damage during postischemic brain reperfusion.

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Regulation of mRNA following brain ischemia and reperfusion

DeGracia

2017

WIREs RNA

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There is growing appreciation that mRNA regulation plays important roles in disease and injury. mRNA regulation and ribonomics occur in brain ischemia and reperfusion (I/R) following stroke and cardiac arrest and resuscitation. It was recognized over 40 years ago that translation arrest (TA) accompanies brain I/R and is now recognized as part of the intrinsic stress responses triggered in neurons. However, neuron death correlates to a prolonged TA in cells fated to undergo delayed neuronal death (DND). Dysfunction of mRNA regulatory processes in cells fated to DND prevents them from translating stress-induced mRNAs such as heat shock proteins. The morphological and biochemical studies of mRNA regulation in postischemic neurons are discussed in the context of the large variety of molecular damage induced by ischemic injury. Open issues and areas of future investigation are highlighted. A sober look at the molecular complexity of ischemia-induced neuronal injury suggests that a network framework will assist in making sense of this complexity. The ribonomic network sits between the gene network and the various protein and metabolic networks. Thus, targeting the ribonomic network may prove more effective at neuroprotection than targeting specific molecular pathways, for which all efforts have failed to the present time to stop DND in stroke and after cardiac arrest. WIREs RNA 2017, 8:e1415. doi: 10.1002/wrna.1415 For further resources related to this article, please visit the WIREs website.

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Brain nuclear DNA survives cardiac arrest and reperfusion

Cited by 21 publications

References 43 publications

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

Brain Mitochondrial DNA Is Not Damaged by Prolonged Cardiac Arrest or Reperfusion

Regulation of mRNA following brain ischemia and reperfusion

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