Long-term effects of brief hypoxia due to cardiac arrest: Hippocampal reductions and memory deficits

Stamenova, Vess; Nicola, Raneen; Aharon‐Peretz, Judith; Goldsher, Dorith; Kapeliovich, Michael; Gilboa, Asaf

doi:10.1016/j.resuscitation.2018.02.016

Cited by 32 publications

(48 citation statements)

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“…Downtime was correlated with volumetric data in order to understand the potential relationship between the duration of hypoxia and cerebral GMV. Unlike other studies which have focused primarily on the hippocampus as a region that is primarily susceptible to hypoxia (Ørbo et al, 2018;Stamenova et al, 2018), our results revealed a strong, negative correlation between the putamen and downtime (partial r = −0.914, p = 0.01). The putamen has been identified as a region that is susceptible to cytotoxic edema in individuals who do not have a favorable outcome from coma after cardiac arrest (Rossetti et al, 2016;Keijzer et al, 2018).…”

Section: Discussioncontrasting

confidence: 99%

“…Such correlations between brain volumes and cognitive function have been observed in other MRI studies of cardiac arrest survivors. Grubb et al (2000) similarly found that, although volumes were reduced in some regions, only total brain volumes were significantly correlated with cognitive performance and Stamenova et al (2018) likewise found that correlations between cognitive functioning and hippocampal volumes were only apparent in their OHCA group, and not within the MI group. One possible explanation could be that pre-existing cerebrovascular disease burden diminishes neural reserve rendering an individual more vulnerable to the effects of cerebral hypoxia.…”

Section: Discussionmentioning

confidence: 91%

“…The neurophysiological correlates of these cognitive deficits may be understood using the selective-vulnerability hypothesis. For example, memory dysfunction has been found to correlate with hippocampal reductions in this population (Stamenova et al, 2018;Ørbo et al, 2019). However, a general pattern of widespread volumetric reduction across cortical (Horstmann et al, 2010;Ørbo et al, 2019) and subcortical structures (Horstmann et al, 2010) are commonly observed.…”

Section: Introductionmentioning

confidence: 99%

“…Most studies of cognitive dysfunction after cardiac arrest have focused on hypoxic/ischemic mechanism, while the contribution of cardiovascular disease to cognitive dysfunction has been relatively overlooked in OHCA survivors (Cronberg and Lilja, 2015). Cardiovascular disease, a risk factor for cardiac arrest, is well known to be associated with cognitive function (Irani et al, 2009;Jefferson et al, 2011;Cronberg and Lilja, 2015), however, few studies have included a cardiovascular control group when examining the neurophysiological and cognitive outcomes in cardiac arrest survivors (Grubb et al, 2000;Stamenova et al, 2018). In the largest known study of cognitive outcomes after cardiac arrest (Lilja et al, 2015), decreased memory performance was observed not only in the cardiac arrest group but also in the myocardial infarction (MI) group that had not experienced an arrest.…”

Section: Introductionmentioning

confidence: 99%

“…Very few MRI studies have focused specifically on OHCA survivors with relatively good neurological outcome (Grubb et al, 2000;Horstmann et al, 2010;Ørbo et al, 2018, 2019Stamenova et al, 2018) even though these individuals are known to experience cognitive deficits. To date, research has understandably focused on survivorship, but with novel medical interventions leading to increased survival rates (Chan et al, 2014), a gap has appeared in our understanding of the residual impacts on the brain caused by cardiac arrest.…”

Section: Introductionmentioning

confidence: 99%

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Exploratory Analyses of Cerebral Gray Matter Volumes After Out-of-Hospital Cardiac Arrest in Good Outcome Survivors

et al. 2020

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Background: Survival rates of cardiac arrest have increased over recent years, however, survivors may still be left with significant morbidity and functional impairment. A primary concern in cardiac arrest survivors is the effect of prolonged hypoxia/ischemia on the brain. The objectives of the present study were threefold: (1) to explore the effect of cardiac arrest on brain gray matter volumes (GMV) in "good outcome" survivors of out-of-hospital cardiac arrest (OHCA), (2) to examine the relationship between GMV, cognitive functioning and arrest factors, and (3) to explore whether OHCA patients differ from a group of patients with myocardial infarction (MI) uncomplicated by cardiac arrest and a group of healthy controls in terms of GMV. Methods: Medically stable OHCA survivors with preserved neurological function and who were eligible for magnetic resonance imaging scanning (MRI; n = 9), were compared to: (1) patients who had experienced a MI (n = 19) and (2) healthy controls (n = 12). Participants underwent brain MRI on a 3T Siemens Trio MRI scanner and GMV was measured by voxel-based morphometry. A comprehensive neuropsychological assessment was also conducted. Global GMV was compared in the three samples using analyses of variance. The relationships between cognition and GMV were examined within group using correlations. Results: The OHCA and MI groups showed a similar pattern of differences compared to the healthy control group. Both groups had decreased GMV in the anterior cingulate cortex, bilateral hippocampus, right dorsolateral prefrontal cortex, right putamen, and bilateral cerebellum. There were no significant differences in global or regional GMV between the OHCA and MI groups. Cognitive functioning was correlated with global GMV in the OHCA group; no such correlation was observed in the MI group. Conclusion: Regional atrophy was observed in OHCA and MI survivors, compared to a healthy control group, suggesting a common mechanism, presumably preexisting cardiovascular disease. Although similar regional volume differences were observed between the MI and OHCA groups, the relationship between GMV and cognition was

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploratory Analyses of Cerebral Gray Matter Volumes After Out-of-Hospital Cardiac Arrest in Good Outcome Survivors

et al. 2020

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Systemic administration of dendrimer N‐acetyl cysteine improves outcomes and survival following cardiac arrest

Modi

Wang

Olmstead

et al. 2021

Bioengineering & Transla Med

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Cardiac arrest (CA), the sudden cessation of effective cardiac pumping function, is still a major clinical problem with a high rate of early and long‐term mortality. Post‐cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer‐N‐acetylcysteine conjugate (D‐NAC), can target “activated” microglial cells following CA, leading to an improvement in post‐CA survival rate compared to saline (86% vs. 45%). D‐NAC treatment also significantly improved gross neurological score within 4 h of treatment ( p < 0.05) and continued to show improvement at 48 h ( p < 0.05). Specifically, there was a substantial impairment in motor responses after CA, which was subsequently improved with D‐NAC treatment ( p < 0.05). D‐NAC also mitigated hippocampal cell density loss seen post‐CA in the CA1 and CA3 subregions ( p < 0.001). These results demonstrate that early therapeutic intervention even with a single D‐NAC bolus results in a robust sustainable improvement in long‐term survival, short‐term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post‐CA syndrome.

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FreeSurfer‐based segmentation of hippocampal subfields: A review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Sämann

Iglesias

Gutman

et al. 2020

Human Brain Mapping

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Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics

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Long-term effects of brief hypoxia due to cardiac arrest: Hippocampal reductions and memory deficits

Cited by 32 publications

References 33 publications

Exploratory Analyses of Cerebral Gray Matter Volumes After Out-of-Hospital Cardiac Arrest in Good Outcome Survivors

Exploratory Analyses of Cerebral Gray Matter Volumes After Out-of-Hospital Cardiac Arrest in Good Outcome Survivors

Systemic administration of dendrimer N‐acetyl cysteine improves outcomes and survival following cardiac arrest

FreeSurfer‐based segmentation of hippocampal subfields: A review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

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