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Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
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Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Genetic variation in complement component C3 shows association with ischaemic stroke.

S Olsson1, A Stokowska, L Holmegaard

  • 1Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. sandra.olsson@neuro.gu.se

European Journal of Neurology
|March 19, 2011
PubMed
Summary

Genetic variations in the third complement component (C3) are linked to ischaemic stroke (IS). This study identified specific C3 gene variants associated with IS risk, independent of common risk factors.

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Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Immunology

Background:

  • Ischaemic stroke (IS) is a leading cause of disability and mortality.
  • The role of genetic factors in IS pathogenesis requires further elucidation.
  • The third complement component (C3) is a key regulator of the complement system, implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the association between genetic variations at the C3 locus and the risk of ischaemic stroke.
  • To determine if specific C3 single nucleotide polymorphisms (SNPs) are risk factors for IS.

Main Methods:

  • Case-control study design involving 844 IS patients and 668 healthy controls.
  • Genotyping of sixteen single nucleotide polymorphisms (SNPs) within the C3 gene.
  • Statistical analysis to assess the association between C3 SNPs and IS, adjusting for covariates.

Main Results:

  • Two C3 SNPs, rs2277984 and rs3745565, demonstrated a significant association with overall IS.
  • SNP rs2277984 was also associated with the cryptogenic stroke subtype.
  • These genetic associations were independent of hypertension, diabetes, and smoking status.
  • The association of rs3745565 with overall IS remained significant after correction for multiple testing.

Conclusions:

  • Genetic variations within the C3 gene are associated with ischaemic stroke in the studied population.
  • C3 genetic polymorphisms may represent novel risk factors or biomarkers for IS.
  • Further research is warranted to explore the functional mechanisms linking C3 variations to stroke.