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Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review).International Journal of Molecular... Feb 2022Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral... (Review)
Review
Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral vessels leads to ischemic strokes, which constitutes the majority of strokes. Ischemic strokes induce brain infarcts, along with cerebral tissue death and focal neuronal damage. The infarct size and neurological severity after ischemic stroke episodes depends on the time period since occurrence, the severity of ischemia, systemic blood pressure, vein systems and location of infarcts, amongst others. Ischemic stroke is a complex disease, and neuronal injuries after ischemic strokes have been the focus of current studies. The present review will provide a basic pathological background of ischemic stroke and cerebral infarcts. Moreover, the major mechanisms underlying ischemic stroke and neuronal injuries are summarized. This review will also briefly summarize some representative clinical trials and up‑to‑date treatments that have been applied to stroke and brain infarcts.
Topics: Animals; Brain Ischemia; Cerebral Infarction; Humans; Ischemic Stroke; Neurons; Neuroprotection; Oxidative Stress
PubMed: 34878154
DOI: 10.3892/ijmm.2021.5070 -
Circulation Jul 2021Over the past few decades, advances in pharmacological, catheter-based, and surgical reperfusion have improved outcomes for patients with acute myocardial infarctions.... (Review)
Review
Over the past few decades, advances in pharmacological, catheter-based, and surgical reperfusion have improved outcomes for patients with acute myocardial infarctions. However, patients with large infarcts or those who do not receive timely revascularization remain at risk for mechanical complications of acute myocardial infarction. The most commonly encountered mechanical complications are acute mitral regurgitation secondary to papillary muscle rupture, ventricular septal defect, pseudoaneurysm, and free wall rupture; each complication is associated with a significant risk of morbidity, mortality, and hospital resource utilization. The care for patients with mechanical complications is complex and requires a multidisciplinary collaboration for prompt recognition, diagnosis, hemodynamic stabilization, and decision support to assist patients and families in the selection of definitive therapies or palliation. However, because of the relatively small number of high-quality studies that exist to guide clinical practice, there is significant variability in care that mainly depends on local expertise and available resources.
Topics: Acute Disease; American Heart Association; Humans; Myocardial Infarction; United States
PubMed: 34126755
DOI: 10.1161/CIR.0000000000000985 -
Circulation Research Jul 2019Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment-elevation myocardial infarction, aiming at... (Review)
Review
Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment-elevation myocardial infarction, aiming at restoring epicardial infarct-related artery patency and achieving microvascular reperfusion as early as possible, thus limiting the extent of irreversibly injured myocardium. Yet, in a sizeable proportion of patients, primary percutaneous coronary intervention does not achieve effective myocardial reperfusion due to the occurrence of coronary microvascular obstruction (MVO). The amount of infarcted myocardium, the so-called infarct size, has long been known to be an independent predictor for major adverse cardiovascular events and adverse left ventricular remodeling after myocardial infarction. Previous cardioprotection studies were mainly aimed at protecting cardiomyocytes and reducing infarct size. However, several clinical and preclinical studies have reported that the presence and extent of MVO represent another important independent predictor of adverse left ventricular remodeling, and recent evidences support the notion that MVO may be more predictive of major adverse cardiovascular events than infarct size itself. Although timely and complete reperfusion is the most effective way of limiting myocardial injury and subsequent ventricular remodeling, the translation of effective therapeutic strategies into improved clinical outcomes has been largely disappointing. Of importance, despite the presence of a large number of studies focused on infarct size, only few cardioprotection studies addressed MVO as a therapeutic target. In this review, we provide a detailed summary of MVO including underlying causes, diagnostic techniques, and current therapeutic approaches. Furthermore, we discuss the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcome following ST-segment-elevation myocardial infarction.
Topics: Adrenergic beta-Antagonists; Animals; Coronary Circulation; Fibrinolytic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Microcirculation; ST Elevation Myocardial Infarction
PubMed: 31268854
DOI: 10.1161/CIRCRESAHA.119.315344 -
Biomechanics and Modeling in... Dec 2023Adverse ventricular remodeling following acute myocardial infarction (MI) may induce ventricular dilation, fibrosis, and loss of global contractile function, possibly...
Adverse ventricular remodeling following acute myocardial infarction (MI) may induce ventricular dilation, fibrosis, and loss of global contractile function, possibly resulting in heart failure (HF). Understanding the relation between the time-dependent changes in material properties of the myocardium and the contractile function of the heart may further our understanding of the development of HF post-MI and guide the development of novel therapies. A finite element model of cardiac mechanics was used to model MI in a thick-walled truncated ellipsoidal geometry. Infarct core and border zone comprised 9.6 and 8.1% of the LV wall volume, respectively. Acute MI was modeled by inhibiting active stress generation. Chronic MI was modeled by the additional effect of infarct material stiffening, wall thinning and fiber reorientation. In acute MI, stroke work decreased by 25%. In the infarct core, fiber stress was reduced but fiber strain was increased, depending on the degree of infarct stiffening. Fiber work density was equal to zero. Healthy tissue adjacent to the infarct showed decreased work density depending on the degree of infarct stiffness and the orientation of the myofibers with respect to the infarct region. Thinning of the wall partially restored this loss in work density while the effects of fiber reorientation were minimal. We found that the relative loss in pump function in the infarcted heart exceeds the relative loss in healthy myocardial tissue due to impaired mechanical function in healthy tissue adjacent to the infarct. Infarct stiffening, wall thinning and fiber reorientation did not affect pump function but did affect the distribution of work density in tissue adjacent to the infarct.
Topics: Humans; Myocardium; Myocardial Infarction; Heart Failure; Heart Ventricles; Ventricular Remodeling
PubMed: 37405536
DOI: 10.1007/s10237-023-01734-1 -
Journal of Molecular and Cellular... Apr 2016Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged... (Review)
Review
Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged during MI is replaced by a collagenous scar over a period of several weeks, and the mechanical properties of that scar tissue are a key determinant of serious post-MI complications such as infarct rupture, depression of heart function, and progression to heart failure. Thus, there is increasing interest in developing therapies that modify the structure and mechanics of healing infarct scar. Yet most prior attempts at therapeutic scar modification have failed, some catastrophically. This article reviews available information about the mechanics of healing infarct scar and the functional impact of scar mechanical properties, and attempts to infer principles that can better guide future attempts to modify scar. One important conclusion is that collagen structure, mechanics, and remodeling of healing infarct scar vary so widely among experimental models that any novel therapy should be tested across a range of species, infarct locations, and reperfusion protocols. Another lesson from past work is that the biology and mechanics of healing infarcts are sufficiently complex that the effects of interventions are often counterintuitive; for example, increasing infarct stiffness has little effect on heart function, and inhibition of matrix metalloproteases (MMPs) has little effect on scar collagen content. Computational models can help explain such counterintuitive results, and are becoming an increasingly important tool for integrating known information to better identify promising therapies and design experiments to test them. Moving forward, potentially exciting new opportunities for therapeutic modification of infarct mechanics include modulating anisotropy and promoting scar compaction.
Topics: Animals; Collagen; Disease Progression; Heart Failure; Heart Ventricles; Humans; Inflammation; Mechanical Phenomena; Myocardial Infarction; Ventricular Remodeling; Wound Healing
PubMed: 26631496
DOI: 10.1016/j.yjmcc.2015.11.028 -
European Neurology 2017MRI is the imaging modality of choice for diagnosing brain infarction. Because of few or atypical clinical symptoms and a relatively low sensitivity of CT scans, many... (Review)
Review
BACKGROUND
MRI is the imaging modality of choice for diagnosing brain infarction. Because of few or atypical clinical symptoms and a relatively low sensitivity of CT scans, many cerebellar infarctions may be detected only with MRI. With adequate recognition of cerebellar infarction on MRI and prompt initiation or optimisation of preventive therapeutic measures, more dramatic strokes may be avoided in selected cases.
SUMMARY
We first briefly review the clinical presentation of cerebellar infarctions, followed by a short refresher on cerebellar anatomy and pathophysiological mechanisms of cerebellar infarcts. Then, we review the arterial cerebellar perfusion territories recently made visible with territorial arterial spin labeling (ASL), followed by a discussion and illustration of the MRI appearance of cerebellar infarcts in different stages. Similar to large cerebellar infarcts, recent studies investigating volumetric MRI datasets have now shown that small cerebellar infarcts occur in typical spatial patterns, knowledge of which may help in the diagnosis of even the smallest of cerebellar infarcts on MRI. Key Messages: MRI is the modality of choice for diagnosing cerebellar infarction. The posterior inferior cerebellar artery (PICA)-territories can be visualised with super-selective territorial ASL MRI. The PICA supplies at least the medial part of the posterior cerebellar surface. Anterior inferior cerebellar artery-infarcts can be mistaken for lateral PICA-infarcts. Small infarcts typically affect the cortex and often present as incidental cavities. Subacute cerebellar infarcts may be missed on imaging due to a phenomenon called "fogging."
Topics: Aged; Cerebellum; Cerebral Infarction; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged
PubMed: 28095387
DOI: 10.1159/000455229 -
International Journal of Environmental... Jul 2022(1) Background: Avascular necrosis (AVN) may affect every part of the bone. Epiphyseal infarcts are likely to be treated early because most are symptomatic. However,... (Review)
Review
(1) Background: Avascular necrosis (AVN) may affect every part of the bone. Epiphyseal infarcts are likely to be treated early because most are symptomatic. However, meta- and diaphyseal infarcts are silent and are diagnosed incidentally. Sarcomas developing in the necrotic bone are extremely rare, but they have been reported in the literature. (2) Methods: We conducted a mapping review of recent evidence regarding these malignancies. Methods: A mapping review using a systematic search strategy was conducted to answer research questions. We limited our research to the last ten years (2012-2022). (3) Results: A total of 11 papers were identified, including 9 case reports and 3 case series. The pathomechanism of carcinogenesis in AVN was not investigated to date. Histologically, most tumors were malignant fibrous histiocytoma. The prognosis is relatively poor, especially for patients with metastases, but adjuvant chemotherapy may increase short- and long-term survival. (4) Conclusions: Since AVN-related malignancies are sporadic, no prospective studies have been conducted. The majority of evidence comes from small case series. More research is needed to identify the risk factors that would justify follow-up of patients after bone infarcts at higher risk of developing a malignancy.
Topics: Bone and Bones; Carcinogenesis; Humans; Infarction; Sarcoma; Soft Tissue Neoplasms
PubMed: 35954639
DOI: 10.3390/ijerph19159282 -
Current Pharmaceutical Design 2014Chemokines are a family of chemotactic cytokines that play an essential role in leukocyte trafficking. Upregulation of both CC and CXC chemokines is a hallmark of the... (Review)
Review
Chemokines are a family of chemotactic cytokines that play an essential role in leukocyte trafficking. Upregulation of both CC and CXC chemokines is a hallmark of the inflammatory and reparative response following myocardial infarction. Release of danger signals from dying cells and damaged extracellular matrix activates innate immune pathways that stimulate chemokine synthesis. Cytokineand chemokine-driven adhesive interactions between endothelial cells and leukocytes mediate extravasation of immune cells into the infarct. CXC chemokines (such as interleukin-8) are bound to glycosaminoglycans on the endothelial surface and activate captured neutrophils, inducing expression of integrins. CC chemokines (such as monocyte chemoattractant protein (MCP)-1) mediate recruitment of proinflammatory and phagocytotic mononuclear cells into the infarct. CC Chemokines may also regulate late infiltration of the healing infarct with inhibitory leukocytes that suppress inflammation and restrain the post-infarction immune response. Non-hematopoietic cells are also targeted by chemokines; in healing infarcts, the CXC chemokine Interferon-γ inducible Protein (IP)-10 exerts antifibrotic actions, inhibiting fibroblast migration. Another member of the CXC subfamily, Stromal cell-derived Factor (SDF)-1, may protect the infarcted heart by activating pro-survival signaling in cardiomyocytes, while exerting angiogenic actions through chemotaxis of endothelial progenitors. Several members of the chemokine family may be promising therapeutic targets to attenuate adverse remodeling in patients with myocardial infarction.
Topics: Animals; Chemokine CXCL12; Chemokines; Chemokines, CXC; Drug Delivery Systems; Humans; Myocardial Infarction
PubMed: 23844733
DOI: 10.2174/13816128113199990449 -
Journal of Cerebral Blood Flow and... Mar 2011Poststroke hyperglycaemia (PSH) is common, has an unclear pathophysiology, and is associated with poor outcomes. Animal studies report conflicting findings. We... (Comparative Study)
Comparative Study Meta-Analysis Review
Poststroke hyperglycaemia (PSH) is common, has an unclear pathophysiology, and is associated with poor outcomes. Animal studies report conflicting findings. We systematically reviewed the effects of hyperglycaemia on infarct volume in middle cerebral artery occlusion (MCAO) models, generating weighted mean differences between groups using random effects models summarised as effect size (normalised to control group infarct volume as 100%) and 95% confidence interval. Of 72 relevant papers, 23 reported infarct volume. Studies involved 664 animals and 35 distinct comparisons. Hyperglycaemia was induced by either streptozotocin (STZ, 17 comparisons, n=303) or dextrose (18 comparisons, n=356). Hyperglycaemic animals had infarcts that were 94% larger, but STZ was associated with significantly greater increase in infarct volumes than dextrose infusion (140% larger versus 48% larger). In seven studies, insulin did not significantly reduce infarct size and results were heterogeneous. Although hyperglycaemia exacerbates infarct volume in MCAO models, studies are heterogeneous, and do not address the common clinical problem of PSH because they have used either the STZ model of type I diabetes or extremely high glucose loads. Insulin had a nonsignificant and significantly heterogeneous effect. Further studies with relevant models may inform clinical trial design.
Topics: Animals; Cerebral Infarction; Glucose; Hyperglycemia; Hypoglycemic Agents; Infarction, Middle Cerebral Artery; Insulin; Streptozocin
PubMed: 21157471
DOI: 10.1038/jcbfm.2010.210 -
Clinical Cardiology Oct 2022This meta-analysis aims to look at the impact of early intravenous Metoprolol in ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary... (Meta-Analysis)
Meta-Analysis Review
Effect of early metoprolol before PCI in ST-segment elevation myocardial infarction on infarct size and left ventricular ejection fraction. A systematic review and meta-analysis of clinical trials.
AIM
This meta-analysis aims to look at the impact of early intravenous Metoprolol in ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) on infarct size, as measured by cardio magnetic resonance (CMR) and left ventricular ejection fraction.
METHODS
We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included only randomized control trials that reported the use of early intravenous Metoprolol in STEMI before PCI on infarct size, as measured by CMR and left ventricular ejection fraction. RevMan software 5.4 was used for performing the analysis.
RESULTS
Following a literature search, 340 publications were found. Finally, 18 studies were included for the systematic review, and 8 clinical trials were included in the meta-analysis after the full-text screening. At 6 months, the pooled effect revealed a statistically significant association between Metoprolol and increased left ventricular ejection fraction (LVEF) (%) compared to controls (mean difference [MD] = 3.57, [95% confidence interval [CI] = 2.22-4.92], p < .00001), as well as decreased infarcted myocardium(g) compared to controls (MD = -3.84, [95% [CI] = -5.75 to -1.93], p < .0001). At 1 week, the pooled effect revealed a statistically significant association between Metoprolol and increased LVEF (%) compared to controls (MD = 2.98, [95% CI = 1.26-4.69], p = .0007), as well as decreased infarcted myocardium(%) compared to controls (MD = -3.21, [95% CI = -5.24 to -1.18], p = .002).
CONCLUSION
A significant decrease in myocardial infarction and increase in LVEF (%) was linked to receiving Metoprolol at 1 week and 6-month follow-up.
Topics: Humans; Metoprolol; Myocardial Infarction; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Stroke Volume; Ventricular Function, Left
PubMed: 36040709
DOI: 10.1002/clc.23894