Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, L. Bierkowski Hospital, Poznan, Poland.
Neurology. 2012 Oct 16;79(16):1677-85. doi: 10.1212/WNL.0b013e31826e9a83. Epub 2012 Sep 19.
To evaluate the significance of circulating tight-junction (TJ) proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke patients.
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.
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.
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.
评估循环紧密连接（TJ）蛋白作为缺血性脑卒中患者出血性转化（HT）预测因子的意义。
我们检查了 458 例连续的缺血性脑卒中患者，其中 7.2%的患者出现临床明显的 HT。所有患者均未接受溶栓治疗。入院时检测血清中血脑屏障（BBB）破坏的标准标志物（S100B、神经元特异性烯醇化酶）、TJ 蛋白（occludin [OCLN]、claudin 5 [CLDN5]、zonula occludens 1 [ZO1]）和 BBB 解体相关分子（基质金属蛋白酶 9 和血管内皮生长因子 [VEGF]）的水平。由 HT 引起的临床恶化（cdHT）定义为 NIH 卒中量表评分增加≥4 分，且在新出现神经症状后立即进行 CT 扫描可见 HT。
与无 cdHT 的患者相比，cdHT 患者的 OCLN、S100B 和 CLDN5/ZO1 比值更高，VEGF 水平更低。CLDN5 水平在卒中发作后 3 小时内估计时，也与 cdHT 的发生相关。我们还发现了循环 TJ 分子水平与 S100B 水平之间的相关性，S100B 是之前已确立的 BBB 破坏标志物。
分析 TJ 蛋白（如 CLDN5、OCLN 和 CLDN5/ZO1 比值）以及 S100B 和 VEGF 的血清水平是筛选缺血性脑卒中患者 HT 引起的临床恶化的有效方法，无论是在 IV 溶栓时间窗内还是之外。
