Chronic mitochondrial dynamic-targeted therapy alleviates left ventricular dysfunction by reducing multiple programmed cell death in post-myocardial infarction rats.

Mitochondrial dysfunction and the activation of multiple programmed cell death (PCD) have been shown to aggravate the severity and mortality associated with the progression of myocardial infarction (MI). Although pharmacological modulation of mitochondrial dynamics, including treatment with the fusion promoter (M1) and the fission inhibitor (Mdivi-1), exerted cardioprotection against several cardiac complications, their roles in the post-MI model have never been investigated. Using a MI rat model instigated by permanent left-anterior descending (LAD) coronary artery occlusion, post-MI rats were randomly assigned to receive one of 4 treatments (n = 10/group): vehicle (DMSO 3%V/V), enalapril (10 mg/kg), Mdivi-1 (1.

Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction.

Background: We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI).

Objective: To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril.

Methods: Male rats were assigned to either sham or MI operation.

Treatment with apoptosis inhibitor restores cognitive impairment in rats with myocardial infarction.

We previously reported that apoptosis is responsible for cognitive impairment in rats with myocardial infarction (MI). Acute administration of an apoptosis inhibitor (Z-vad) effectively reduced brain inflammation in rats with cardiac ischemia/reperfusion injury. However, the beneficial effects of Z-vad on cognitive function, brain inflammation, mitochondrial function, cell death pathways, and neurogenesis in MI rats have not been investigated.

GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement.

Background: Myocardial infarction (MI) has recently accounted for more than one-third of global mortality. Multiple molecular pathological pathways, such as oxidative stress, inflammation, and mitochondrial dysfunction, have been recognized as possible mechanisms in the development of MI. Furthermore, different phases of ischemic injury following the progression of MI were also associated with multiple types of programmed cell death (PCDs), including apoptosis, necroptosis, ferroptosis, and pyroptosis.

Mild Cognitive impairment Occurs in Rats During the Early Remodeling Phase of Myocardial Infarction.

Cognitive impairment is a common health problem among people with heart failure (HF). Increases in oxidative stress, brain inflammation, and microglial hyperactivity have been reported in preclinical models of myocardial infarction (MI)-induced HF. We tested the hypothesis that oxidative stress, brain inflammation, mitochondrial dysfunction, and cell death participate in cognitive impairment in the early remodeling phase of MI.

Necrostatin-1 reduces cardiac and mitochondrial dysfunction in prediabetic rats.

High-fat diet (HFD) consumption induces prediabetes and left ventricular dysfunction through many pathways including cell death pathway like necroptosis. Although the benefit of necroptosis inhibitor (necrostatin-1 or Nec-1) in the brain of prediabetic rats was shown, the effects of Nec-1 on cardiac autonomic function, blood pressure, cardiac function, along with its mechanistic insight have not been investigated. Male Wistar rats were fed with either a normal diet (n = 8) or HFD (n = 24) for 12 weeks to induce prediabetes.

Cognitive impairment in myocardial infarction and heart failure.

Myocardial infarction (MI) occurs when coronary blood flow is decreased due to an obstruction/occlusion of the vessels, leading to myocardial death and progression to heart failure (HF). Cognitive impairment, anxiety, depression and memory loss are the most frequent mental health problems among patients with HF. The most common cause of cognitive decline is cardiac systolic dysfunction, which leads to reduced cerebral perfusion.

Not only metformin, but also D-allulose, alleviates metabolic disturbance and cognitive decline in prediabetic rats.

Background: Prediabetes can be characterized as obesity with metabolic disturbance, leading to cognitive decline and brain pathologies. D-allulose administration in obese animals decreased metabolic disturbance. However, the comparative effects of D-allulose and metformin on cognition and brain functions in the diet-induced prediabetic condition are unclear.

D-allulose provides cardioprotective effect by attenuating cardiac mitochondrial dysfunction in obesity-induced insulin-resistant rats.

Purpose: Obesity-induced insulin resistant is associated with cardiovascular diseases via impairing cardiac mitochondria. Recently, D-allulose could protect β-islets and improve insulin resistance. However, the effects of D-allulose on the heart and cardiac mitochondrial function under obesity-induced insulin-resistant condition has not been investigated.

Necrostatin-1 Mitigates Cognitive Dysfunction in Prediabetic Rats With No Alteration in Insulin Sensitivity.

Previous studies showed that 12 weeks of high-fat diet (HFD) consumption caused not only prediabetes but also cognitive decline and brain pathologies. Recently, necrostatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated.