Ischemia and stroke
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Understanding Ischemia and Stroke: Pathophysiology, Risk Factors, and Therapeutic Approaches
Introduction to Ischemic Stroke
Ischemic stroke, a leading cause of death and disability worldwide, occurs due to the occlusion of a cerebral blood vessel, leading to brain infarction. The severity and outcome of an ischemic stroke depend on various factors, including the duration and severity of ischemia, collateral circulation, systemic blood pressure, and patient-specific factors such as age, sex, comorbidities, and genetic background.
Pathophysiological Mechanisms in Ischemic Stroke
Cellular and Molecular Pathways
The brain injury following an ischemic stroke is a result of complex pathophysiological events, including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis. These processes are influenced by interactions between brain ischemia, immune cells, intracranial atherosclerosis, and the gut microbiota. Additionally, ischemia-reperfusion injury, which occurs when blood flow is restored to the ischemic tissue, can exacerbate tissue damage through mechanisms such as cell death and hemorrhagic transformation.
Neuronal Cell Death Pathways
Multiple cell death pathways are implicated in the pathogenesis of ischemic stroke, including intrinsic and extrinsic apoptosis, necroptosis, autophagy, ferroptosis, parthanatos, phagoptosis, and pyroptosis. Understanding these pathways is crucial for developing neuroprotective interventions.
Risk Factors and Global Burden
Major Risk Factors
Ischemic stroke is influenced by several risk factors, including smoking, high body mass index (BMI), high systolic blood pressure, high low-density lipoprotein cholesterol, kidney dysfunction, high fasting plasma glucose, and high sodium diet. These factors contribute significantly to the global disease burden of ischemic stroke.
Global Trends and Predictions
From 1990 to 2019, the global number of ischemic stroke deaths increased from 2.04 million to 3.29 million and is projected to rise to 4.90 million by 2030. The burden is particularly high in low socio-demographic index (SDI) regions and among young people.
Experimental Models and Therapeutic Approaches
Experimental Models
Various experimental models are used to study ischemic stroke, including the endovascular suture model, endothelin-1-induced focal ischemia, and photothrombotic stroke models. These models help in understanding the molecular pathways and testing potential therapeutic interventions.
Established Treatments
Current treatments for acute ischemic stroke include intravenous thrombolysis with alteplase within 4.5 hours of symptom onset and early administration of aspirin. Patients benefit from close monitoring in specialized stroke units and, in some cases, early decompressive surgery for space-occupying infarcts.
Emerging Therapeutic Targets
Research is ongoing to identify novel therapeutic targets by understanding the cellular and molecular changes following ischemic stroke. Potential targets include pathways involved in blood-brain barrier integrity, endothelial cell function, and the role of pericytes and immune cells. Additionally, metabolome-based techniques are being explored to identify biomarkers and develop new diagnostic and therapeutic approaches.
Conclusion
Ischemic stroke is a complex and multifaceted disease with significant global health implications. Understanding the pathophysiological mechanisms, identifying major risk factors, and developing effective therapeutic strategies are crucial for reducing the burden of this debilitating condition. Ongoing research and experimental models continue to provide valuable insights into the underlying mechanisms and potential treatments for ischemic stroke.
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