Biocompatible BSA–MnO2 nanoparticles for in vivo timely permeability imaging of blood–brain barrier and prediction of hemorrhage transformation in acute ischemic stroke

Nanoscale ◽  
2021 ◽  
Author(s):  
Wenjing Hou ◽  
Yingzong Jiang ◽  
Guangchao Xie ◽  
Lu Zhao ◽  
Fangshi Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Attractive Potential ◽  
Blood Brain ◽  
Mno2 Nanoparticles

Biocompatible BSA–MnO2 nanoparticles hold an attractive potential as alternative MR nanoprobes for the theranostics of stroke.

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.

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