Lasek-Bal Anetta, Kokot Anna, Gendosz de Carrillo Daria, Student Sebastian, Pawletko Katarzyna, Krzan Aleksandra, Puz Przemysław, Bal Wiesław, Jędrzejowska-Szypułka Halina
Department of Neurology, School of Health Sciences, Medical University of Silesia, 40-055 Katowice, Poland.
Department of Neurology, Upper-Silesia Medical Center, Stroke Interventional Therapy Center, 40-635 Katowice, Poland.
Brain Sci. 2020 Nov 9;10(11):831. doi: 10.3390/brainsci10110831.
The blood-brain barrier is the structure (BBB), which isolates the central nervous system from the external environmental. During a stroke, the BBB gets damaged, which is accompanied by changes in the concentrations and distributions of claudin-5, occludin, ZO-1, and other building blocks of the BBB. The aim of this study was to assess the concentrations of selected components of the BBB-occludin, claudin-5, and zonulin (ZO-1)-and to define a potential relationship between the concentrations of these three substances and the type of stroke, the location and extent of the infarct focus, the neurological/functional status in the acute phase of the disease, and the patient's clinical profile.
In this prospective study, we qualified patients with first-in-life stroke. All patients were analyzed according to: the presence of comorbidities, type of stroke (OCSP), treatment type in the first day of hospitalization, hemorrhagic transformation of infarct focus (ECASS), neurological status on the first day of stroke (NIHSS), functional status (mRS) on the ninth day of disease. In all patients, the plasma concentrations of claudin-5, occludin, and ZO-1 on the first day of stroke were examined and next, the mean concentrations were analyzed and compared between subgroups created on the basis of demographical and clinical features.
The mean concentration of occludin was significantly higher in patients with partial anterior cerebral infarct (PACI) compared to patients with posterior cerebral infarct (POCI; 1.03 vs. 0.66 ng/mL; = 0.009) and in patients with location of ischemic stroke in the carotid artery supply compared with in the vertebrobasilar supply (respectively: 1.036 vs. 0.660 ng/mL; = 0.009). The mean concentration of claudin 5 was significantly higher in patients with PACI compared to patients with POCI (0.37 vs. 0.21 ng/mL; = 0.011) and in patients with location of ischemic stroke in the carotid artery supply in comparison with vertebrobasilar supply (respectively: 0.373 vs. 0.249 ng/mL; = 0.011). The differences in mean occludin and claudin 5 concentrations between female and male were statistically not significant, similarly between patients < 65 years and older. A significantly higher mean concentration of zonulin was observed in patients > 65 years of age compared to younger patients (0.59 vs. 0.48 ng/mL; = 0.010) and in patients with arterial hypertension compared to patients without the disease (0.63 ng/mL vs. 0.26 ng/mL; = 0.026). There were no statistically significant relationships between the concentration of occludin, claudin 5, and zonulin and the neurological status according to the NIHSS on the first day of stroke.
The location of stroke in the anterior part of the brain's blood supply is associated with high blood levels of occludin and claudin 5 in the acute phase of stroke. The blood concentration of occludin is significantly lower in lacunar stroke comparing to this in non-lacunar stroke. Old age and arterial hypertension correlate positively with the concentration of zonulin 1 in acute stroke. There is no relationship between the blood levels of occludin, claudin 5, and zonulin 1 on the first day of stroke and the neurological and functional status in the acute phase of the disease.
血脑屏障是一种将中枢神经系统与外部环境隔离开的结构(BBB)。中风期间,血脑屏障会受损,同时紧密连接蛋白-5、闭合蛋白、紧密连接蛋白-1(ZO-1)以及血脑屏障的其他组成部分的浓度和分布也会发生变化。本研究的目的是评估血脑屏障的特定组成部分——闭合蛋白、紧密连接蛋白-5和闭合蛋白(ZO-1)的浓度,并确定这三种物质的浓度与中风类型、梗死灶的位置和范围、疾病急性期的神经/功能状态以及患者的临床特征之间的潜在关系。
在这项前瞻性研究中,我们纳入了首次发生中风的患者。所有患者均根据以下因素进行分析:合并症的存在、中风类型(OCSP)、住院第一天的治疗类型、梗死灶的出血转化(ECASS)、中风第一天的神经状态(NIHSS)、疾病第九天的功能状态(mRS)。在所有患者中,检测了中风第一天血浆中紧密连接蛋白-5、闭合蛋白和紧密连接蛋白-1的浓度,然后分析并比较了根据人口统计学和临床特征划分的亚组之间的平均浓度。
与后脑梗死(POCI)患者相比,部分前脑梗死(PACI)患者的闭合蛋白平均浓度显著更高(1.03对0.66 ng/mL;P = 0.009),且与椎基底动脉供血区缺血性中风患者相比,颈动脉供血区缺血性中风患者的闭合蛋白平均浓度更高(分别为1.036对0.660 ng/mL;P = 0.009)。与POCI患者相比,PACI患者的紧密连接蛋白5平均浓度显著更高(0.37对0.21 ng/mL;P = 0.011),且与椎基底动脉供血区缺血性中风患者相比,颈动脉供血区缺血性中风患者的紧密连接蛋白5平均浓度更高(分别为0.373对0.249 ng/mL;P = 0.011)。女性和男性之间闭合蛋白和紧密连接蛋白5的平均浓度差异无统计学意义,65岁以下和65岁以上患者之间也是如此。与年轻患者相比,65岁以上患者的闭合蛋白平均浓度显著更高(0.59对0.48 ng/mL;P = 0.010),与无高血压疾病的患者相比,高血压患者的闭合蛋白平均浓度更高(0.63 ng/mL对0.26 ng/mL;P = 0.026)。中风第一天,根据NIHSS评估,闭合蛋白、紧密连接蛋白5和闭合蛋白的浓度与神经状态之间无统计学显著关系。
脑供血前部中风的位置与中风急性期闭合蛋白和紧密连接蛋白5的高血水平相关。与非腔隙性中风相比,腔隙性中风患者的闭合蛋白血浓度显著更低。老年和动脉高血压与急性中风中闭合蛋白1的浓度呈正相关。中风第一天,闭合蛋白、紧密连接蛋白5和闭合蛋白1的血水平与疾病急性期的神经和功能状态之间无关系。