Biochemical Markers for Blood-Brain Barrier Dysfunction in Acute Ischemic Stroke Correlate with Evolution and Outcome

2011 ◽  
Vol 65 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Raf Brouns ◽  
Annick Wauters ◽  
Didier De Surgeloose ◽  
Peter Mariën ◽  
Peter P. De Deyn
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Biochemical Markers ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

scholarly journals Effects of fasudil on blood-brain barrier integrity

2021 ◽  
Author(s):  
Kei Sato ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Yuki Matsunaga ◽  
Takashi Fujimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Tight Junction ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Tight Junction Protein ◽  
Brain Barrier ◽  
Blood Brain ◽  
Junction Protein ◽  
Culture Models

Abstract Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Medhods: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6-hour OGD/24-hour reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using immunohistochemistry and western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3–30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.

Early Blood Brain Barrier Changes in Acute Ischemic Stroke: A Sequential MRI Study

2015 ◽  
Vol 25 (6) ◽  
pp. 959-963 ◽  
Author(s):  
Marc Giraud ◽  
Tae-Hee Cho ◽  
Norbert Nighoghossian ◽  
Delphine Maucort-Boulch ◽  
Gianluca Deiana ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mri Study

Blood-Brain Barrier Protection as a Therapeutic Strategy for Acute Ischemic Stroke

2017 ◽  
Vol 19 (4) ◽  
pp. 957-972 ◽  
Author(s):  
Ali Ehsan Sifat ◽  
Bhuvaneshwar Vaidya ◽  
Thomas J. Abbruscato
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Therapeutic Strategy ◽  
Brain Barrier ◽  
Blood Brain

Early Blood‐Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke

2018 ◽  
Vol 28 (3) ◽  
pp. 283-288 ◽  
Author(s):  
Zhong‐Song Shi ◽  
Gary R. Duckwiler ◽  
Reza Jahan ◽  
Satoshi Tateshima ◽  
Viktor Szeder ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Mechanical Thrombectomy ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

Abstract TP340: The Level of Occludin in Blood as a Potential Biomarker for Blood-Brain Barrier Damage and Predicting Hemorrhage Transformation After Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Zhifeng Qi ◽  
Ke Jian Liu
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Infarction ◽  
Critical Role ◽  
Onset Time ◽  
Brain Barrier ◽  
Cerebral Microvessels ◽  
Blood Brain ◽  
Potential Biomarker

Fear of hemorrhage transformation (HT) has been the primary reason for withholding the effective recanalization therapies (thrombolysis or thrombectomy) from most acute ischemic stroke (AIS) patients. Currently there is no reliable indicator available to predict HT before recanalization. The degradation of tight junction proteins plays a critical role in blood-brain barrier (BBB) disruption in ischemic stroke. We hypothesize that since occludin fragment in peripheral blood is derived from the degradation of occludin on cerebral microvessels, elevated blood occludin level directly reflects BBB disruption and may serve as a biomarker for BBB damage to predict the risk of HT after recanalization. In this study, we determined occludin fragment in the blood of rats, non-human primates and human patients after AIS using ELISA assay, and evaluated its level with BBB damage, HT, and other neurological outcomes. We found that ischemia induced rapid occludin degradation and BBB disruption, while occludin fragment was released into the blood circulation. Cerebral ischemia resulted in a dramatic increase of occludin fragments in rat blood samples after 4-hr ischemia, which was correlated well with occludin loss from ischemic cerebral microvessels. In the blood sample from ischemic rhesus monkeys, occludin level significantly increased after 2h ischemia from baseline, which correlated well with brain infarction shown in MRI images. We further collected the sera of AIS patients as early as they arrived at hospital. Our results indicated that the level of occludin increased in accord with ischemia onset time and neurological dysfunctions. The level of blood occludin in AIS patients with HT was much higher that those without HT. Together, our findings from rats, non-human primates and patients suggest that the level of occludin fragment in blood could serve as a biomarker for HT and neurological outcome following AIS, which could be used to safely guide recanalization for AIS in the clinic.

scholarly journals Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke

2020 ◽  
Vol 13 (626) ◽  
pp. eaay5686 ◽  
Author(s):  
Feifei Ma ◽  
Ping Sun ◽  
Xuejing Zhang ◽  
Milton H. Hamblin ◽  
Ke-Jie Yin
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Neuronal Loss ◽  
Glucose Deprivation ◽  
Brain Barrier ◽  
Protein Abundance ◽  
Barrier Dysfunction ◽  
Small Noncoding Rnas ◽  
Blood Brain

The blood-brain barrier (BBB) maintains a stable brain microenvironment. Breakdown of BBB integrity during cerebral ischemia initiates a devastating cascade of events that eventually leads to neuronal loss. MicroRNAs are small noncoding RNAs that suppress protein expression, and we previously showed that the miR-15a/16-1 cluster is involved in the pathogenesis of ischemic brain injury. Here, we demonstrated that when subjected to experimentally induced stroke, mice with an endothelial cell (EC)–selective deletion of miR-15a/16-1 had smaller brain infarcts, reduced BBB leakage, and decreased infiltration of peripheral immune cells. These mice also showed reduced infiltration of proinflammatory M1-type microglia/macrophage in the peri-infarct area without changes in the number of resolving M2-type cells. Stroke decreases claudin-5 abundance, and we found that EC-selective miR-15a/16-1 deletion enhanced claudin-5 mRNA and protein abundance in ischemic mouse brains. In cultured mouse brain microvascular ECs (mBMECs), the miR-15a/16-1 cluster directly bound to the 3′ untranslated region (3′UTR) of Claudin-5, and lentivirus-mediated ablation of miR-15a/16-1 diminished oxygen-glucose deprivation (OGD)–induced down-regulation of claudin-5 mRNA and protein abundance and endothelial barrier dysfunction. These findings suggest that genetic deletion of endothelial miR-15a/16-1 suppresses BBB pathologies after ischemic stroke. Elucidating the molecular mechanisms of miR-15a/16-1–mediated BBB dysfunction may enable the discovery of new therapies for ischemic stroke.

scholarly journals Blood-brain barrier dysfunction and recovery after ischemic stroke

2018 ◽  
Vol 163-164 ◽  
pp. 144-171 ◽  
Author(s):  
Xiaoyan Jiang ◽  
Anuska V. Andjelkovic ◽  
Ling Zhu ◽  
Tuo Yang ◽  
Michael V.L. Bennett ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain
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