Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients

Neurology ◽  
2012 ◽  
Vol 79 (16) ◽  
pp. 1677-1685 ◽  
Author(s):  
R. Kazmierski ◽  
S. Michalak ◽  
A. Wencel-Warot ◽  
W. L. Nowinski
Keyword(s):  
Ischemic Stroke ◽  
Tight Junction ◽  
Hemorrhagic Transformation ◽  
Tight Junction Proteins ◽  
Stroke Patients ◽  
Junction Proteins

scholarly journals MicroRNA-30a regulates acute cerebral ischemia-induced blood–brain barrier damage through ZnT4/zinc pathway

2020 ◽  
pp. 0271678X2092678 ◽  
Author(s):  
Peng Wang ◽  
Rong Pan ◽  
John Weaver ◽  
Mengjie Jia ◽  
Xue Yang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Blood Brain ◽  
Acute Cerebral Ischemia ◽  
Junction Proteins

The mechanism of early blood–brain barrier (BBB) disruption after stroke has been intensively studied but still not fully understood. Here, we report that microRNA-30a (miR-30a) could mediate BBB damage using both cellular and animal models of ischemic stroke. In the experiments in vitro, inhibition of miR-30a decreased BBB permeability, prevented the degradation of tight junction proteins, and reduced intracellular free zinc in endothelial cells. We found that the zinc transporter ZnT4 was a direct target of negative regulation by miR-30a, and ZnT4/zinc signaling pathway contributed significantly to miR-30a-mediated BBB damage. Consistent with these in vitro findings, treatment with miR-30a inhibitor reduced zinc accumulation, increased the expression of ZnT4, and prevented the loss of tight junction proteins in microvessels of ischemic animals. Furthermore, inhibition of miR-30a, even at 90 min post onset of middle cerebral artery occlusion, prevented BBB damage, reduced infarct volume, and ameliorated neurological deficits. Together, our findings provide novel insights into the mechanisms of cerebral ischemia-induced BBB disruption and indicate miR-30a as a regulator of BBB function that can be an effective therapeutic target for ischemic stroke.

scholarly journals Early Electroacupuncture Extends the rtPA Time Window to 6 h in a Male Rat Model of Embolic Stroke via the ERK1/2-MMP9 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xin-chang Zhang ◽  
Ya-hui Gu ◽  
Wen-tao Xu ◽  
Yang-yang Song ◽  
Ao Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Edema ◽  
Time Window ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Hemorrhagic Transformation ◽  
Male Rat ◽  
Tight Junction Proteins ◽  
Therapeutic Time Window ◽  
Junction Proteins

Background. Recombinant tissue plasminogen activator (rtPA) is the only recommended pharmacological treatment for acute ischemic stroke, but it has a restricted therapeutic time window. When administered at time points greater than 4.5 h after stroke onset, rtPA disrupts the blood-brain barrier (BBB), which leads to serious brain edema and hemorrhagic transformation. Electroacupuncture (EA) exerts a neuroprotective effect on cerebral ischemia; however, researchers have not clearly determined whether EA increases the safety of thrombolysis and extends the therapeutic time window of rtPA administration following ischemic stroke. Objective. The present study was conducted to test the hypothesis that EA extends the therapeutic time window of rtPA for ischemic stroke in a male rat model of embolic stroke. Methods. SD rats were randomly divided into the sham operation group, model group, rtPA group, EA+rtPA group, and rtPA+MEK1/2 inhibitor group. An injection of rtPA was administered 6 h after ischemia. Rats were treated with EA at the Shuigou (GV26) and Neiguan (PC6) acupoints at 2 h after ischemia. Neurological function, infarct volume, BBB permeability, brain edema, and hemorrhagic transformation were assessed at 24 h after ischemia. Western blotting and immunofluorescence staining were performed to detect the levels of proteins involved in the ERK1/2 signaling pathway (MEK1/2 and ERK1/2), tight junction proteins (Claudin5 and ZO-1), and MMP9 in the ischemic penumbra at 24 h after stroke. Results. Delayed rtPA treatment aggravated hemorrhagic transformation and brain edema. However, treatment with EA plus rtPA significantly improved neurological function and reduced the infarct volume, hemorrhagic transformation, brain edema, and EB leakage in rats compared with rtPA alone. EA increased the levels of tight junction proteins, inhibited the activation of the ERK1/2 signaling pathway, and reduced MMP9 overexpression induced by delayed rtPA thrombolysis. Conclusions. EA potentially represents an effective adjunct method to increase the safety of thrombolytic therapy and extend the therapeutic time window of rtPA administration following ischemic stroke. This neuroprotective effect may be mediated by the inhibition of the ERK1/2-MMP9 pathway and alleviation of the destruction of the BBB.

Tight junction proteins in HCC and metastatic liver tumours

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
Cs Páska ◽  
E Orbán ◽  
A Kiss ◽  
Zs Schaff ◽  
A Szijjártó ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junction Proteins ◽  
Liver Tumours ◽  
Metastatic Liver ◽  
Junction Proteins

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

New insights in gut-liver axis in wild-type murine imiquimod-induced lupus

Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 926-936
Author(s):  
Georges Maalouly ◽  
Joelle Hajal ◽  
Charbel Noujeim ◽  
Michel Choueiry ◽  
Hussein Nassereddine ◽  
...  
Keyword(s):  
Tight Junction ◽  
Fecal Calprotectin ◽  
Liver Inflammation ◽  
Tight Junction Proteins ◽  
Wild Type ◽  
Imiquimod Cream ◽  
E Coli ◽  
Intestinal Pathology ◽  
Nfκb Pathway ◽  
Junction Proteins

Background Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated. Objective This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus. Methods C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and E. coli protein in liver were assessed at sacrifice. Results At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression. Conclusion This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.

scholarly journals Stress hyperglycemia as a prognostic factor in acute ischemic stroke patients: a prospective observational cohort study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hanaa A. El-Gendy ◽  
Mahmoud A. Mohamed ◽  
Amr E. Abd-Elhamid ◽  
Mohammed A. Nosseir
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Prognostic Value ◽  
Area Under The Curve ◽  
Hemorrhagic Transformation ◽  
Diabetic Patients ◽  
Stroke Patients ◽  
Stress Hyperglycemia ◽  
Discrimination Power ◽  
Observational Cohort

Abstract Background Hyperglycemia is a risk factor for infarct expansion and poor outcome for both diabetic and non-diabetic patients. We aimed to study the prognostic value of stress hyperglycemia on the outcome of acute ischemic stroke patients as regards National Institutes of Health Stroke Scale (NIHSS) as a primary outcome. Results Patients with high random blood sugar (RBS) on admission showed significantly higher values of both median NIHSS score and median duration of hospital stay. There were significant associations between stress hyperglycemia and the risk of 30-day mortality (p < 0.001), the need for mechanical ventilation (p < 0.001) and vasopressors (p < 0.001), and the occurrence of hemorrhagic transformation (p = 0.001). The 24-h RBS levels at a cut off > 145 mg/dl showed a significantly good discrimination power for 30-day mortality (area under the curve = 0.809). Conclusions Stress hyperglycemia had a prognostic value and was associated with less-favorable outcomes of acute stroke patients. Therefore, early glycemic control is recommended for those patients.

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