Understanding physiologic phospholipid maintenance in the context of brain mitochondrial phospholipid alterations after cardiac arrest

Kuschner, Cyrus E.; Kim, Nancy; Shoaib, Muhammad Harris; Choudhary, Rishabh; Nishikimi, Mitsuaki; Yin, Tai; Becker, Lance B.; Hoppel, Charles L.; Kim, Junhwan

doi:10.1016/j.mito.2021.08.009

Cited by 9 publications

(9 citation statements)

References 30 publications

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“…With the global IRI caused by CA, most patients are unable to survive with those who do having severe brain injury 3 . Prior studies have demonstrated that brain mitochondria are severely injured both structurally and functionally resulting in brain damage 5,6,38,39 …”

Section: Discussionmentioning

confidence: 99%

“…3 Prior studies have demonstrated that brain mitochondria are severely injured both structurally and functionally resulting in brain damage. 5,6,38,39 Therefore, mitigating brain mitochondrial damage post-CA is an important avenue of exploration when developing interventions for treating CA. With its high safety profile and substantial efficacy in treating diabetes, metformin has also shown multiple beneficial effects in other diseases, such as aging, cancer, and ischemia.…”

Section: Discussionmentioning

confidence: 99%

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Metformin‐mediated mitochondrial protection post‐cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

et al. 2022

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Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. The small population of surviving patients suffer extensive brain damage that results in substantial morbidity. Mitochondrial dysfunction in most organs after CA has been implicated as a major source of injury. Metformin, a first‐line treatment for diabetes, has shown promising results in the treatment for other diseases and is known to interact with the mitochondria. For the treatment of CA, prior studies have utilized metformin in a preconditioning manner such that animals are given metformin well before undergoing CA. As the timing of CA is quite difficult to predict, the present study, in a clinically relevant manner, sought to evaluate the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial‐CA rat model. This is the first study to show that metformin treatment post‐CA (a) improves 72 h survival and neurologic function, (b) protects mitochondrial function with a reduction in apoptotic brain injury without activating AMPK, and (c) potentiates earlier normalization of brain electrophysiologic activity. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metformin‐mediated mitochondrial protection post‐cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

et al. 2022

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“…For instance, decrease of mitochondrial PE content in mice has been shown to be harmful on cell survival, oxygen consumption, and ATP production ( van der Veen et al, 2017 ). Moreover, PC has also been considered to be an independent risk factor for atherosclerosis ( Kuschner et al, 2021 ). In the current study, we found apparent decline of serum phospholipids in MIR mice, which was reversed by XJEK treatment.…”

Section: Discussionmentioning

confidence: 99%

Xin-Ji-Er-Kang protects heart from ischemia-reperfusion injury by rebalancing lipid metabolism

et al. 2022

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Background and Purpose: We have previously reported a cardioprotective effect with Xin-Ji-Er-Kang (XJEK) treatment in mice with myocardial infarction (MI)-induced heart failure, but no report about its potential functions in myocardial ischemia-reperfusion (MIR) injury. Here we studied the therapeutic effects of XJEK on MIR injury and investigated the mechanisms involved.Experimental Approach: MIR model of Balb/c mice induced by left anterior descending coronary artery ligation for half an hour, followed by reperfusion, was utilized to study the potential therapeutic effects of XJEK on MIR-induced cardiac injury. Ultra-performance liquid chromatography tandem Orbitrap mass spectrometry platform was used for studying serum lipid metabolic signatures.Key Results: MIR caused cardiac dysfunctions, cardiac injury, myocardial fibrosis, and increased inflammation, and all the observed abnormalities caused by MIR were largely corrected by XJEK treatment. Mechanistically, XJEK exerts its cardioprotective effect in the context of MIR injury by suppressing MIR-induced inflammation and dysregulation of serum lipid metabolism.Conclusion and Implications: We have demonstrated for the first time that XJEK protects heart from MIR injury by restoring dysregulated lipidomics. Our data provide new evidence to support a therapeutic effect for XIEK on MIR-induced cardiac injury, and pave the way for exploring the therapeutic potential of XJEK in large animal study and early clinical trial.

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“…Brain damage post-CA has been implicated as a major source of poor outcomes. Furthermore, the brain mitochondria are severely injured in that their membrane lipid composition is altered 6,40 as well as disruption of proper function in the energy generation centers 5,41 . As such, mitigating brain mitochondrial damage post-CA is an important avenue of exploration in developing interventions for treating CA.…”

Section: Discussionmentioning

confidence: 99%

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

Shoaib

Choudhary

Chillale

et al. 2021

Preprint

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Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. Surviving patients suffer extensive brain damage with mitochondrial dysfunction implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has also shown promising results in other diseases and is known to interact with mitochondria. In the present study, we evaluated the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA a) improves survival and neurologic function, b) potentiates early normalization of brain electrophysiologic activity, and c) protects mitochondrial function with a reduction in apoptotic brain injury. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.

show abstract

Understanding physiologic phospholipid maintenance in the context of brain mitochondrial phospholipid alterations after cardiac arrest

Cited by 9 publications

References 30 publications

Metformin‐mediated mitochondrial protection post‐cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

Metformin‐mediated mitochondrial protection post‐cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

Xin-Ji-Er-Kang protects heart from ischemia-reperfusion injury by rebalancing lipid metabolism

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

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