Plasma Levels of Occludin and Claudin-5 in Acute Stroke Are Correlated with the Type and Location of Stroke but Not with the Neurological State of Patients—Preliminary Data

Abstract

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. Methods: 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. Results: 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; p = 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; p = 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; p = 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; p = 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; p = 0.010) and in patients with arterial hypertension compared to patients without the disease (0.63 ng/mL vs. 0.26 ng/mL; p = 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. Conclusions: 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.

Claudin-5 relieves cognitive decline in Alzheimer’s disease mice through suppression of inhibitory GABAergic neurotransmission

“…We then examined claudin-5 level from hippocampal tissues of these mice and found a decrease of claudin-5 both in protein (t = 1.263; P = 0.021; Figure 1C , 1D ) and mRNA level (t = 1.013; P = 0.003; Figure 1E ). To investigate if supplementation of claudin-5 had effects on cognitive ability of APP/PS1 mice, we intravenously injected different concentration of claudin-5 (1, 2, 4 μM) [ 31 , 32 ] into the APP/PS1 mice. We found that intravenous injection of claudin-5 at 4 μM but not 1 or 2 μM restored decreased claudin-5 mRNA level (F 4,25 = 35.845; P = 0.041; Figure 2A ) without affecting other claudins ( Supplementary Figure 1A ) in APP/PS1 mice of the hippocampal region.…”

Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson’s Disease: Preclinical and Clinical Studies

“…Rifaximin treatment significantly reduced the serum concentrations of proinflammatory cytokines IL-1β, IL-6, and TNF-α in the MitoPark mice (representative image, Figure 2 A and analysis, Figure 2 B, Supplementary Figure S1 for the full blot). Furthermore, the rifaximin-treated MitoPark mice had a significant reduction in blood claudin-5 and occludin, which are markers of BBB permeabilization [ 26 , 27 ] (representative image in Figure 2 C and analysis results in Figure 2 D). These results suggested that the robust anti-inflammatory effect of rifaximin prevented leaky gut syndrome-associated systemic inflammation and subsequent BBB permeabilization.…”

Appearance of claudin-5+ leukocyte subtypes in the blood and CNS during progression of EAE

“…After an initial drop from the level in naïve animals, CLN-5 + MFI in both blood and CNS trended upward gradually from D6 to D12, then peaked sharply at D15. As at or around this time of disease there is heightened inflammation, when TJs are being broken down and considerable CLN-5 protein is lost from the CNS vasculature [ 21 , 44 , 45 ], B cells may have acquired some CLN-5 protein that was liberated into the circulation, the inter-endothelial cleft, and/or perivascular space through proteolysis or other means [ 46 , 47 ].…”