Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area. Genetic, cellular, and tissue engineering therapies are promising avenues but require days/months for permitting proper functional tissue regeneration. Here we engineered biocompatible silicon carbide semiconductive nanowires that synthetically couple, via membrane nanobridge formations, isolated beating cardiomyocytes over distance, restoring physiological cell-cell conductance, thereby permitting the synchronization of bioelectrical activity in otherwise uncoupled cells. Local in-situ multiple injections of nanowires in the left ventricular infarcted regions allow rapid reinstatement of impulse propagation across damaged areas and recover electrogram parameters and conduction velocity. Here we propose this nanomedical intervention as a strategy for reducing ventricular arrhythmia after acute myocardial infarction.

Characteristics and mechanism of reciprocal ST-segment depression in acute ST segment elevation myocardial infarction

Background: At present, the mechanism of reciprocal ST-segment depression(RSTD) is still not clear.Methods: The electrocardiogram and angiography of 85 STEMI patients were retrospectively analyzed to summarize the characteristics of ST segment changes and explore the mechanism of RSTD.Results: A total of 85 patients were included, of which 75 were patients with RSTD (10 patients with anterior myocardial infarction had no RSTD), all 45 patients with inferior myocardial infarction had limb leads RSTD, and 37 of them had anterior lead ST segment depression.Thirty patients with anterior myocardial infarction were accompanied by mild ST segment changes in the limb leads. According to the characteristics of RSTD, it is speculated that the mechanism of RSTD is that the action potential of infarct area decreased , which could not offset the action potential in non-infarct area.Conclusion: the mechanism of RSTD in acute myocardial infarction maybe that the negative electrode action potential of the lead was weakened or disappeared, and the positive electrode action potential could not be completely offset, resulting in ST segment depression.

Transient Focal Cerebral Ischemia Leads to miRNA Alterations in Different Brain Regions, Blood Serum, Liver, and Spleen

Ischemic stroke is characterized by an occlusion of a cerebral blood vessel resulting in neuronal cell death due to nutritional and oxygen deficiency. Additionally, post-ischemic cell death is augmented after reperfusion. These events are paralleled by dysregulated miRNA expression profiles in the peri-infarct area. Understanding the underlying molecular mechanism in the peri-infarct region is crucial for developing promising therapeutics. Utilizing a tMCAo (transient Middle Cerebral Artery occlusion) model in rats, we studied the expression levels of the miRNAs (miR) 223-3p, 155-5p, 3473, and 448-5p in the cortex, amygdala, thalamus, and hippocampus of both the ipsi- and contralateral hemispheres. Additionally, the levels in the blood serum, spleen, and liver and the expression of their target genes, namely, Nlrp3, Socs1, Socs3, and Vegfa, were assessed. We observed an increase in all miRNAs on the ipsilateral side of the cerebral cortex in a time-dependent manner and increased miRNAs levels (miR-223-3p, miR-3473, and miR-448-5p) in the contralateral hemisphere after 72 h. Besides the cerebral cortex, the amygdala presented increased expression levels, whereas the thalamus and hippocampus showed no alterations. Different levels of the investigated miRNAs were detected in blood serum, liver, and spleen. The gene targets were altered not only in the peri-infarct area of the cortex but selectively increased in the investigated non-affected brain regions along with the spleen and liver during the reperfusion time up to 72 h. Our results suggest a supra-regional influence of miRNAs following ischemic stroke, which should be studied to further identify whether miRNAs are transported or locally upregulated.

Effectiveness of atorvastatin in acute atherothrombotic cerebral infarction

Introduction: Cerebrovascular Diseases (CVD) constitute one of the most important health problems on a global scale and in Cuba they occupy the third cause of death and the first cause of disability. Objective: To evaluate the use of atorvastatin in the acute phase of atherothrombotic cerebral infarction. Method: A prospective longitudinal study was carried out in patients who attended the on-call department of the Julio Trigo López Hospital and were diagnosed with acute atherothrombotic cerebral infarction, who were randomly administered with prior informed consent: 0, 20 mg or 40 mg of atorvastatin , they underwent CAT (Computerized Axial Tomography) of the skull, which was repeated on the third day and at 30 days, the value of PCR (C Reactive Protein) was determined in on-call body, on the fifth day and at 30 days, they were clinically evaluated according to the NIHSS scale (National Institute of Health Stroke Scale) in on-call body , daily during their admission and 30 days later. Results: The size of the infarct area decreased by 19.4% with 40 mg of atorvastatin as did the CRP value which was reduced by 16 mg/Ll. The clinical assessment (NIHSS scale) was reduced according to the dose of atorvastatin by slightly more than 8 points. Conclusions: The decrease in infarct area was directly proportional to the dose of atorvastatin used, just as the CRP values were lower and the favorable clinical evolution was associated with the use of this.

MiR-122-5p Attenuates Endothelial-to-Mesenchymal Transition Induced by Oxygen and Glucose Deprivation/Reperfusion

Endothelial-to-mesenchymal transition (EndoMT) is a common phenomenon in vascular diseases, while the role of endothelial dysfunction in central vascular disease remains to be further investigated. MiR-122 is an inflammation-associated non-coding RNA that participates in multiple human disease, but whether miR-122 plays as a critical role in EndoMT induced by ischaemic stroke is unknown. Although BAI2 is known as a brain-specific inhibitor protein of angiogenesis, few studies of BAI2 examined EndoMT. This study investigated the mechanism of EndoMT and the miR-122/BAI2 axis in oxygen-glucose deprivation/reperfusion (OGD/R)-mediated EndoMT. A transient middle cerebral artery occlusion (tMCAO) model and OGD/R treatment were used to mimic the ischaemia-reperfusion injury. The colocalization of CD31 and α-SMA was elevated in the peri-infarct area of tMCAO mice. The expression of miR-122 was decreased in the peri-infarct area of tMCAO mice. Downregulation of miR-122, Occludin, and ZO-1 was observed in human brain microvascular endothelial cells (HBMECs) after OGD/R treatment, while α-SMA expression was increased in HBMECs after OGD/R treatment. MiR-122 overexpression reduced the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. MiR-122 negatively regulated BAI2 expression, and OGD/R treatment enhanced BAI2 expression. Knockdown the expression of BAI2 suppressed the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. In conclusion, miR-122 overexpression attenuates OGD/R-mediated EndoMT by targeting BAI2.

Zuogui Pill Attenuates Neuroinflammation and Improves Cognitive Function in Cerebral Ischemia Reperfusion-Injured Rats

<b><i>Introduction:</i></b> Cerebral ischemia and reperfusion (CI/R) injury is a devasting cerebrovascular disease, accompanied with ischemia stroke, cerebral infarction. Zuogui Pill (ZGP), as a Chinese traditional medicine, is proved to be effective in many diseases and cancers. Our study aimed to detect the roles of ZGP in CI/R injury. <b><i>Methods:</i></b> Neural stem cells were isolated from rats and induced by oxygen and glucose deprivation and recovery. CCK-8 and flow cytometry were applied to assess the function of ZGP on cell viability and apoptosis. Rat CI/R injury models were established by the middle cerebral artery occlusion and reperfusion. The function of ZGP on CI/R injury was identified via evaluating modified neurological severity score, infarct area, and cognitive impairment. <b><i>Results:</i></b> Compared to the control, the cell viability was obviously decreased in the oxygen and glucose deprivation and recovery (OGD/R) group, while the adverse influence on cells was reversed by cultured plus 10% ZGP serum. Consistently, ZGP attenuated the influence of OGD/R on cell apoptosis. More importantly, ZGP could alleviate CI/R injury of rats by reducing neurological damage and infarct area and promoting cognitive function. <b><i>Conclusion:</i></b> This study provided protective roles of ZGP on cell viability and apoptosis induced by OGD/R. In addition, ZGP played protective roles on neuroinflammation and cognitive function in rats.

Cardioprotective Effect of Pretreatment with A Single High-Dose Atorvastatin via Regulating Myocardial Uncoupling Protein 3 in a Rat Ischemia/Reperfusion Model

Objective: Since ischemia/reperfusion (I/R) can cause malignant arrhythmia, we explored the cardioprotective effect of pretreatment with a single and large dose of atorvastatin in the SD rat model. Methods: Rats were distributed into atorvastatin (Ator), I/R model and sham groups (n = 8/group) by random number table method. In Ator group, atorvastatin was gavaged with a single dose (80 mg/kg) 12 h before I/R. The heart was treated with ischemia for 30 min and then reperfusion for 2 h. Results: Myocardial infarct area was induced by I/R when compared with Sham group. Compared with I/R group, the pretreatment of atorvastatin significantly reduced area at risk/left ventricle (40.78 ± 1.39% vs. 46.76 ± 1.42%, p < 0.01), infarct area/area at risk (21.47 ± 1.65% vs. 29.16 ± 1.21%, p < 0.01), and lactate dehydrogenase activity (3056.17 ± 136.22 RFU vs. 3864.15 ± 162.92 RFU, p < 0.05). I/R induced uncoupling protein 3 (UCP3) in transcriptional and translational levels, but atorvastatin significantly increased the UCP3 expression when compared with I/R group, 1.91 ± 0.42 vs. 1.42 ± 0.21 fold (p < 0.05) in mRNA levels measured by RT-PCR and 2.07 ± 0.18 versus 1.45 ± 0.23 fold in protein levels by Western blots. Conclusion: A single high-dose atorvastatin pretreatment 12 h before I/R reduces the infarct area in I/R model in rats. The cardioprotection may be via regulating myocardial UCP3.

Intravital imaging of cerebral microinfarct reveals an astrocyte reaction led to glial scar

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular-level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular-level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2-3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte-vessel coverage and extravascular leakage indicating blood-brain barrier (BBB) dysfunction. At day 5, edema disappeared with recovery of pericyte-vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen-rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes appeared at the peri-infarct area early at day 2 and thereafter accumulated in the peri-infarct. Oral administration of a reversible monoamine oxidase B inhibitor significantly decreased the astrocyte reactivity and fibrous scar formation. Our result suggests that astrocyte reactivity may be a key target to alleviate the impact of microinfarction.

Characteristics and mechanism of reciprocal ST-segment depression in acute ST segment elevation myocardial infarction

Background:At present, the mechanism of reciprocal ST-segment depression(RSTD) is still not clear. Purpose : We proposed the mechanism of RSTD: the action potential of negative electrode of the lead was weakened or disappeared, and the AP of positive electrode could not be completely offset. The electrocardiograms of patients with acute STEMI were analyzed to explore the mechanism of RSTD. Methods: The electrocardiogram and angiography of 85 STEMI patients were retrospectively analyzed to summarize the characteristics of ST segment changes. Results: A total of 85 patients were included, of which 75 were patients with RSTD (10 patients with anterior myocardial infarction had no RSTD), all 45 patients with inferior myocardial infarction had limb leads RSTD, and 37 of them had anterior lead ST segment depression.Thirty patients with anterior myocardial infarction were accompanied by mild ST segment changes in the limb leads. According to the characteristics of RSTD, it is speculated that the mechanism of RSTD is that the action potential of infarct area decreased , which could not offset the action potential in non-infarct area. By using this mechanism, all ST segment changes in STEMI can be explained by the proposed mechanism, and the value of the ST segment changes can be calculated in limb leads. Conclusion: the mechanism of RSTD in acute myocardial infarction is that the negative electrode action potential of the lead was weakened or disappeared, and the positive electrode action potential could not be completely offset, resulting in ST segment depression.

Plasticity-Enhancing Effects of Levodopa Treatment after Stroke

Dopaminergic treatment in combination with rehabilitative training enhances long-term recovery after stroke. However, the underlying mechanisms on structural plasticity are unknown. Here, we show an increased dopaminergic innervation of the ischemic territory during the first week after stroke induced in Wistar rats subjected to transient occlusion of the middle cerebral artery (tMCAO) for 120 min. This response was also found in rats subjected to permanent focal ischemia induced by photothrombosis (PT) and mice subjected to PT or tMCAO. Dopaminergic branches were detected in the infarct core of mice and rats in both stroke models. In addition, the Nogo A pathway was significantly downregulated in rats treated with levodopa (LD) compared to vehicle-treated animals subjected to tMCAO. Specifically, the number of Nogo A positive oligodendrocytes as well as the levels of Nogo A and the Nogo A receptor were significantly downregulated in the peri-infarct area of LD-treated animals, while the number of Oligodendrocyte transcription factor 2 positive cells increased in this region after treatment. In addition, we observed lower protein levels of Growth Associated Protein 43 in the peri-infarct area compared to sham-operated animals without treatment effect. The results provide the first evidence of the plasticity-promoting actions of dopaminergic treatment following stroke.