Interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest

Wang, Jianjie; Li, Jingru; Chen, Bihua; Shen, Yiming; Wang, Juan; Wang, Kaifa; Yin, Changchun; Li, Yongqin

doi:10.1186/s12872-021-02262-5

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…A limitation to take into account is that only male rats were included in our analyses. Considering that sex dimorphism occurs in many aspects of the brain, including in experimental and clinical cases of ACA and stroke, [70][71][72] examining the effect of exercised post-ACA female rats would strengthen the current findings and these studies are underway in our laboratory. In addition, although we focused on memory as the main cognitive outcome of PE post-ACA, the multiple operations of the cells rescued by PE suggest that many other functions are probably preserved.…”

Section: Discussionmentioning

confidence: 58%

Post cardiac arrest physical exercise mitigates cell death in the septal and thalamic nuclei and ameliorates contextual fear conditioning deficits in rats

Ferrier

Saul

Khoury

et al. 2022

J Cereb Blood Flow Metab

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A major concern for cardiac arrest (CA) survivors is the manifestation of long-term cognitive impairments. Physical exercise (PE) is a well-established approach to improve cognitive functions under certain pathological conditions. We previously showed that PE post-CA mitigates cognitive deficits, but the underlying mechanisms remain unknown. To define neuroprotective mechanisms, we analyzed whether PE post-CA protects neurons involved in memory. We first performed a contextual fear conditioning (CFC) test to confirm that PE post-CA preserves memory in rats. We then conducted a cell-count analysis and determined the number of live cells in the hippocampus, and septal and thalamic nuclei, all areas involved in cognitive functions. Lastly, we performed RNA-seq to determine PE post-CA effect on gene expression. Following CA, exercised rats had preserved CFC memory than sham PE animals. Despite this outcome, PE post-CA did not protect hippocampal cells from dying. However, PE ameliorated cell death in septal and thalamic nuclei compared to sham PE animals, suggesting that these nuclei are crucial in mitigating cognitive decline post-CA. Interestingly, PE affected regulation of genes related to neuroinflammation, plasticity, and cell death. These findings reveal potential mechanisms whereby PE post-CA preserves cognitive functions by protecting septal and thalamic cells via gene regulation.

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Section: Discussionmentioning

confidence: 58%

Post cardiac arrest physical exercise mitigates cell death in the septal and thalamic nuclei and ameliorates contextual fear conditioning deficits in rats

Ferrier

Saul

Khoury

et al. 2022

J Cereb Blood Flow Metab

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“…Second, postresuscitation lung injury was only evaluated for a shorter duration of 4 h, which was difficult to fully confirm the effectiveness of SFN in alleviating postresuscitation lung injury. Third, considering that the sex has been shown to be an influencing factor on the effectiveness of organ protection provided by postresuscitation interventions in the previous studies (36,37), only the male pigs were chosen to use in this study. Thus, the effectiveness of SFN in alleviating postresuscitation lung injury remains to be investigated in a female pig model.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Alleviates Postresuscitation Lung Pyroptosis Possibly via Activating the Nrf2/Ho-1 Pathway

Li,

Yang,

Xie

et al. 2023

Shock

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Introduction Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion following cardiac arrest and resuscitation. Methods After animal preparation, twenty-four pigs were randomly divided into Sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 ml of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase (SOD), the contents of malondialdehyde (MDA), interleukin-1β (IL-1β), and interleukin-18 (IL-18), and the expression levels of NOD-like receptor pyrin domain 3 (NLRP3), cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal (GSDMD-N), Nrf2, and HO-1. Results During CPR, spontaneous circulation was achieved in 6 and 7 pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and OI) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (SOD, MDA), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis-related proteins (NLRP3, cleaved caspase 1, GSDMD, GSDMD-N), and activated the Nrf2/HO-1 pathway when compared to the CPR group. Conclusions SFN produced effective post-resuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.

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“…First, a dose of 4.5 mg/kg of tubastatin A administered at 5 minutes after resuscitation provided effective protection for myocardial dysfunction after CA/CPR in swine; however, its optimal dosage and feasible therapeutic windows were not investigated in this animal study. Second, considering that the sex may affect the outcome of CPR according to the previous studies, 32 , 33 only male swine were used in the present study. Thus, it is unknown whether postresuscitation myocardial protection could be achieved by tubastatin A treatment in a female swine of CA and resuscitation.…”

Section: Discussionmentioning

confidence: 99%

Tubastatin A Improves Post‐Resuscitation Myocardial Dysfunction by Inhibiting NLRP3‐Mediated Pyroptosis Through Enhancing Transcription Factor EB Signaling

Zhao

Jiang

et al. 2022

JAHA

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Background Myocardial dysfunction is the leading cause of early death following successful cardiopulmonary resuscitation (CPR) in people with cardiac arrest (CA), which is potentially driven by cell pyroptosis mediated by NOD‐like receptor pyrin domain 3 (NLRP3) inflammasome. Recently, histone deacetylase 6 (HDAC6) inhibition was shown to exert effective myocardial protection against regional ischemia/reperfusion injury. In this study, we investigated whether tubastatin A, a specific histone deacetylase 6 inhibitor, could improve postresuscitation myocardial dysfunction through the inhibition of NLRP3‐mediated cell pyroptosis and its modulation mechanism. Methods and Results Healthy male white domestic swine were used to establish the model of CA/CPR in vivo, and the H9c2 cardiomyocyte hypoxia/reoxygenation model was used to simulate the CA/CPR process in vitro. Consequently, tubastatin A inhibited NLRP3 inflammasome activation, decreased proinflammatory cytokines production and cell pyroptosis, and increased cell survival after hypoxia/reoxygenation in H9c2 cardiomyocytes in vitro. In addition, tubastatin A increased the acetylated levels of transcription factor EB and its translocation to the nucleus, and its protective effect above was partly abrogated by transcription factor EB short interfering RNA after hypoxia/reoxygenation in H9c2 cardiomyocytes. Similarly, tubastatin A promoted cardiac transcription factor EB nuclear translocation, inhibited NLRP3‐mediated cell pyroptosis, and mitigated myocardial dysfunction after CA/CPR in swine. Conclusions The inhibition of histone deacetylase 6 activity by tubastatin A limited NLRP3 inflammasome activation and cell pyroptosis probably through the enhancement of transcription factor EB signaling, and therefore improved myocardial dysfunction after CA/CPR.

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Interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest

Cited by 8 publications

References 37 publications

Post cardiac arrest physical exercise mitigates cell death in the septal and thalamic nuclei and ameliorates contextual fear conditioning deficits in rats

Post cardiac arrest physical exercise mitigates cell death in the septal and thalamic nuclei and ameliorates contextual fear conditioning deficits in rats

Sulforaphane Alleviates Postresuscitation Lung Pyroptosis Possibly via Activating the Nrf2/Ho-1 Pathway

Tubastatin A Improves Post‐Resuscitation Myocardial Dysfunction by Inhibiting NLRP3‐Mediated Pyroptosis Through Enhancing Transcription Factor EB Signaling

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