title: Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients.
abstract: OBJECTIVE
  To evaluate the significance of circulating tight-junction (TJ) proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke patients.
  
  
  METHODS
  We examined 458 consecutive ischemic stroke patients, 7.2% of whom had clinically evident HT. None of the patients was treated with thrombolytic drugs. Serum levels of standard markers of blood-brain barrier (BBB) breakdown (S100B, neuron-specific enolase), TJ proteins (occludin [OCLN], claudin 5 [CLDN5], zonula occludens 1 [ZO1]), and molecules involved in BBB disintegration (matrix metalloproteinase 9 and vascular endothelial growth factor [VEGF]) were assessed upon admission to the emergency department. A clinical deterioration caused by HT (cdHT) was defined as an increase of ≥4 points in the NIH Stroke Scale score in combination with a visible HT on a CT scan performed immediately after the onset of new neurologic symptoms.
  
  
  RESULTS
  Patients with cdHT had higher concentrations of OCLN, S100B, and the CLDN5/ZO1 ratio, and a lower level of VEGF than those without cdHT. CLDN5 levels also correlated with cdHT occurrence when estimated within 3 hours of stroke onset. We also demonstrated correlations between the levels of circulating TJ molecules and the level of S100B, which is a previously established marker of BBB disruption.
  
  
  CONCLUSIONS
  Analyzing serum levels of TJ proteins, like CLDN5, OCLN, and CLDN5/ZO1 ratio, as well as S100B and VEGF, is an effective way to screen for clinical deterioration caused by HT in ischemic stroke patients, both within and after the IV thrombolysis time window.
authors.affiliation: Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, L. Bierkowski Hospital, Poznan, Poland. rkazmierski@ump.edu.pl
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Kazmierski
authors.forename: Slawomir
authors.initials: S
authors.lastname: Michalak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wencel-Warot
authors.forename: Wieslaw L
authors.initials: WL
authors.lastname: Nowinski
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000209:etiology; D062507:Claudin-5 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D009422:Nervous System Diseases / Q000209:etiology; D062793:Occludin / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D020521:Stroke / Q000097:blood* / Q000150:complications; D019108:Tight Junctions / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000097:blood
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D062507:Claudin-5; D009414:Nerve Growth Factors; D062793:Occludin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; D020780:Matrix Metalloproteinase 9; D010751:Phosphopyruvate Hydratase