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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 -
Laeknabladid May 2014Eight of ten strokes are due to cerebral ischemia, two from cerebal hemorrhage. Stroke is the most common cause of disability, the second commonest cause of dementia and... (Review)
Review
Eight of ten strokes are due to cerebral ischemia, two from cerebal hemorrhage. Stroke is the most common cause of disability, the second commonest cause of dementia and the fourth commonest cause of death in the developed world. The incidence of stroke is 150-200/100.000 individuals/ year. One of every seven individuals suffers from stroke in their lifetime. In this article the epidemiology, risk factors, pathophysiology and symptoms of cerebral ischemia will be reviewed.
Topics: Brain Ischemia; Cerebral Angiography; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; Humans; Incidence; Predictive Value of Tests; Prognosis; Risk Factors; Stroke
PubMed: 24846950
DOI: 10.17992/lbl.2014.05.543 -
Cells Jul 2020Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain... (Review)
Review
Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain tissue damage, including neuronal cell death and cerebral infarction, manifesting clinically as ischemic stroke, which is the cause of considerable morbidity and mortality worldwide. To analyze the underlying biological mechanisms and identify potential biomarkers of ischemic stroke, various in vitro and in vivo experimental models have been established investigating different molecular aspects, such as genes, microRNAs, and proteins. Yet, the metabolic and cellular pathologies of ischemic brain injury remain not fully elucidated, and the relationships among various pathological mechanisms are difficult to establish due to the heterogeneity and complexity of the disease. Metabolome-based techniques can provide clues about the cellular pathologic status of a condition as metabolic disturbances can represent an endpoint in biological phenomena. A number of investigations have analyzed metabolic changes in samples from cerebral ischemia patients and from various in vivo and in vitro models. We previously analyzed levels of amino acids and organic acids, as well as polyamine distribution in an in vivo rat model, and identified relationships between metabolic changes and cellular functions through bioinformatics tools. This review focuses on the metabolic and cellular changes in cerebral ischemia that offer a deeper understanding of the pathology underlying ischemic strokes and contribute to the development of new diagnostic and therapeutic approaches.
Topics: Animals; Brain Ischemia; Humans; Infarction, Middle Cerebral Artery; Metabolome; Metabolomics
PubMed: 32645907
DOI: 10.3390/cells9071630 -
ELife Apr 2023Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic...
Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.
Topics: Mice; Humans; Animals; Exosomes; Induced Pluripotent Stem Cells; Brain Ischemia; Cerebral Infarction; Cell Differentiation; Ischemic Stroke
PubMed: 37104115
DOI: 10.7554/eLife.84493 -
Annals of Medicine Dec 2023Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative...
Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX in the I/R was revealed. Using the I/R rat model, the effects of DEX and the copper chelator D-penicillamine on cerebral infarct volume, copper levels, mitochondrial respiration and membrane potential, GSH content, and enrichment of cuproptosis functional proteins were examined. The involvement of ferredoxin 1 (FDX1) in the DEX regulatory pathway was verified by overexpressing FDX1 . DEX could significantly reduce cerebral infarction in rats, reduce copper levels, maintain mitochondrial functions, increase GSH, and reduce the content of key proteins related to cuproptosis. These aspects were replicated and revealed that FDX1 overexpression partially reversed the impacts of DEX. Together, cuproptosis occurs in the brain I/R process and DEX can enhance cell survival by blocking the primary pathway mediated by FDX1.KEY MESSAGESDexmedetomidine reduces cerebral infarction in the I/R rat models.Dexmedetomidine reduces cuproptosis in the I/R rat models.FDX1, an upstream of protein fatty acylation, mediates regulation of Dexmedetomidine.
Topics: Animals; Rats; Apoptosis; Brain Ischemia; Cerebral Infarction; Dexmedetomidine; Ferredoxins; Homeostasis; Reperfusion; Reperfusion Injury
PubMed: 37162502
DOI: 10.1080/07853890.2023.2209735 -
Journal of Cerebral Blood Flow and... Oct 2022Brain ischemia affects all ages, from neonates to the elderly population, and is a leading cause of mortality and morbidity. Multiple preclinical rodent models involving... (Review)
Review
Brain ischemia affects all ages, from neonates to the elderly population, and is a leading cause of mortality and morbidity. Multiple preclinical rodent models involving different ages have been developed to investigate the effect of ischemia during different times of key brain maturation events. Traditional models of developmental brain ischemia have focused on rodents at postnatal day 7-10, though emerging models in juvenile rodents (postnatal days 17-25) indicate that there may be fundamental differences in neuronal injury and functional outcomes following focal or global cerebral ischemia at different developmental ages, as well as in adults. Here, we consider the timing of injury in terms of excitation/inhibition balance, oxidative stress, inflammatory responses, blood brain barrier integrity, and white matter injury. Finally, we review translational strategies to improve function after ischemic brain injury, including new ideas regarding neurorestoration, or neural repair strategies that restore plasticity, at delayed time points after ischemia.
Topics: Aged; Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Cerebral Infarction; Disease Models, Animal; Humans; Ischemia
PubMed: 35765984
DOI: 10.1177/0271678X221111600 -
Nature Communications Feb 2024Aneurysmal subarachnoid haemorrhage (aSAH) presents a challenge to clinicians because of its multisystem effects. Advancements in computed tomography (CT), endovascular... (Review)
Review
Aneurysmal subarachnoid haemorrhage (aSAH) presents a challenge to clinicians because of its multisystem effects. Advancements in computed tomography (CT), endovascular treatments, and neurocritical care have contributed to declining mortality rates. The critical care of aSAH prioritises cerebral perfusion, early aneurysm securement, and the prevention of secondary brain injury and systemic complications. Early interventions to mitigate cardiopulmonary complications, dyselectrolytemia and treatment of culprit aneurysm require a multidisciplinary approach. Standardised neurological assessments, transcranial doppler (TCD), and advanced imaging, along with hypertensive and invasive therapies, are vital in reducing delayed cerebral ischemia and poor outcomes. Health care disparities, particularly in the resource allocation for SAH treatment, affect outcomes significantly, with telemedicine and novel technologies proposed to address this health inequalities. This article underscores the necessity for comprehensive multidisciplinary care and the urgent need for large-scale studies to validate standardised treatment protocols for improved SAH outcomes.
Topics: Humans; Subarachnoid Hemorrhage; Brain Ischemia; Cerebral Infarction; Hypertension; Aneurysm
PubMed: 38424037
DOI: 10.1038/s41467-024-46015-2 -
Neurocritical Care Oct 2023Delayed cerebral ischemia (DCI) is a major determinant for poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). Detection and treatment of DCI is a... (Review)
Review
INTRODUCTION
Delayed cerebral ischemia (DCI) is a major determinant for poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). Detection and treatment of DCI is a key component in the neurocritical care of patients with aSAH after initial aneurysm repair.
METHODS
Narrative review of the literature.
RESULTS
Over the past 2 decades, there has been a paradigm shift away from macrovascular (angiographic) vasospasm as a main diagnostic and therapeutic target. Instead, the pathophysiology of DCI is hypothesized to derive from several proischemic pathomechanisms. Clinical examination remains the most reliable means for monitoring and treatment of DCI, but its value is limited in comatose patients. In such patients, monitoring of DCI is usually based on numerous neurophysiological and/or radiological diagnostic modalities. Catheter angiography remains the gold standard for the detection of macrovascular spasm. Computed tomography (CT) angiography is increasingly used instead of catheter angiography because it is less invasive and may be combined with CT perfusion imaging. CT perfusion permits semiquantitative cerebral blood flow measurements, including the evaluation of the microcirculation. It may be used for prediction, early detection, and diagnosis of DCI, with yet-to-prove benefit on clinical outcome when used as a screening modality. Transcranial Doppler may be considered as an additional noninvasive screening tool for flow velocities in the middle cerebral artery, with limited accuracy in other cerebral arteries. Continuous electroencephalography enables detection of early signs of ischemia at a reversible stage prior to clinical manifestation. However, its widespread use is still limited because of the required infrastructure and expertise in data interpretation. Near-infrared spectroscopy, a noninvasive and continuous modality for evaluation of cerebral blood flow dynamics, has shown conflicting results and needs further validation. Monitoring techniques beyond neurological examinations may help in the detection of DCI, especially in comatose patients. However, these techniques are limited because of their invasive nature and/or restriction of measurements to focal brain areas.
CONCLUSION
The current literature review underscores the need for incorporating existing modalities and developing new methods to evaluate brain perfusion, brain metabolism, and overall brain function more accurately and more globally.
Topics: Humans; Subarachnoid Hemorrhage; Coma; Cerebral Infarction; Brain Ischemia; Tomography, X-Ray Computed; Vasospasm, Intracranial
PubMed: 37537496
DOI: 10.1007/s12028-023-01812-3 -
Experimental Neurology Jun 2017Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain... (Review)
Review
Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia currently being employed to study diabetes-related ischemic brain damage. The rational use of such animal systems in studying the disease condition may better help evaluate novel therapeutic approaches for diabetes related exacerbation of ischemic brain damage.
Topics: Animals; Brain Ischemia; Cerebral Infarction; Diabetes Mellitus; Disease Models, Animal; Humans; Stroke
PubMed: 28274862
DOI: 10.1016/j.expneurol.2017.03.004 -
International Journal of Molecular... Mar 2022Delayed cerebral ischemia (DCI) remains a challenging but very important condition, because DCI is preventable and treatable for improving functional outcomes after... (Review)
Review
Delayed cerebral ischemia (DCI) remains a challenging but very important condition, because DCI is preventable and treatable for improving functional outcomes after aneurysmal subarachnoid hemorrhage (SAH). The pathologies underlying DCI are multifactorial. Classical approaches to DCI focus exclusively on preventing and treating the reduction of blood flow supply. However, recently, glutamate-mediated neuroelectric disruptions, such as excitotoxicity, cortical spreading depolarization and seizures, and epileptiform discharges, have been reported to occur in high frequencies in association with DCI development after SAH. Each of the neuroelectric disruptions can trigger the other, which augments metabolic demand. If increased metabolic demand exceeds the impaired blood supply, the mismatch leads to relative ischemia, resulting in DCI. The neuroelectric disruption also induces inverted vasoconstrictive neurovascular coupling in compromised brain tissues after SAH, causing DCI. Although glutamates and the receptors may play central roles in the development of excitotoxicity, cortical spreading ischemia and epileptic activity-related events, more studies are needed to clarify the pathophysiology and to develop novel therapeutic strategies for preventing or treating neuroelectric disruption-related DCI after SAH. This article reviews the recent advancement in research on neuroelectric disruption after SAH.
Topics: Brain Ischemia; Cerebral Infarction; Epilepsy; Humans; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 35328523
DOI: 10.3390/ijms23063102