Pathophysiology of stroke
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Pathophysiology of Stroke
Introduction to Stroke Pathophysiology
Stroke is a leading cause of death and disability worldwide, with ischemic stroke being the most prevalent type. The pathophysiology of stroke involves a complex interplay of hemodynamic, molecular, and systemic factors that contribute to brain injury and subsequent neurological deficits 124.
Hemodynamic Factors in Stroke
Cerebral Blood Flow and Ischemia
Stroke occurs due to a critical reduction in cerebral blood flow, often resulting from the obstruction of a large brain artery. This reduction leads to focal ischemia, where the brain tissue is deprived of oxygen and glucose, essential for cellular function . The regulation of blood flow and the role of collateral circulation are crucial in determining the extent of ischemic damage .
The Ischemic Penumbra
The concept of the ischemic penumbra is central to understanding stroke pathophysiology. The penumbra is the area surrounding the infarct core that suffers milder insults and retains some viability. This region is a target for therapeutic interventions aimed at salvaging brain tissue and improving outcomes 28.
Molecular Mechanisms of Injury
Excitotoxicity and Calcium Overload
Following ischemia, prolonged activation of excitatory neurotransmitter receptors leads to intracellular calcium accumulation, which triggers a cascade of events resulting in neuronal death. This process, known as excitotoxicity, is a primary mechanism of early brain injury in stroke 59.
Inflammation and Apoptosis
Inflammatory responses play a significant role in stroke pathophysiology. The release of pro-inflammatory cytokines and the activation of immune cells contribute to secondary brain injury. Additionally, apoptosis, or programmed cell death, occurs in the ischemic penumbra, further exacerbating tissue damage 4910.
Systemic Responses to Stroke
Peripheral Immune System and Organ Dysfunction
Stroke induces systemic pathophysiological responses, including peripheral immunodepression and hyperstimulation of autonomic and neuroendocrine pathways. These responses can lead to dysfunction in various organ systems, such as the respiratory, cardiovascular, and gastrointestinal systems, significantly impacting morbidity and mortality .
Age and Sex Differences
Age and sex are critical factors influencing stroke risk, pathology, and outcomes. Aging is the strongest nonmodifiable risk factor, with older patients experiencing higher mortality and poorer recovery. Additionally, sex differences affect stroke incidence and severity, with men being more affected early in life and women in older age .
Advances in Stroke Research
Therapeutic Targets and Novel Interventions
Recent research has focused on identifying new molecular targets for stroke therapy. These include signaling proteins involved in excitotoxicity, inflammation, and neuroprotection. Understanding these pathways can lead to the development of novel therapeutic strategies aimed at improving stroke outcomes 47.
The Role of the Neurovascular Unit
The neurovascular unit, comprising various brain cell types, plays a crucial role in stroke pathophysiology. The interaction between these cells and peripheral immune cells influences the extent of brain injury and recovery. Comprehensive treatment approaches targeting both brain and systemic effects are essential for improving stroke outcomes .
Conclusion
The pathophysiology of stroke is a multifaceted process involving hemodynamic, molecular, and systemic factors. Advances in understanding these mechanisms have highlighted potential therapeutic targets and the importance of comprehensive treatment strategies. Continued research is essential to develop effective therapies that can mitigate the devastating impact of stroke on patients and healthcare systems.
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