scholarly journals Comparative effects of dexmedetomidine and propofol on brain and lung damage in experimental acute ischemic stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giselle C. Sousa ◽  
Marcos Vinicius Fernandes ◽  
Fernanda F. Cruz ◽  
Mariana A. Antunes ◽  
Carla M. da Silva ◽  
...  

AbstractAcute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8–15.3) vs. 19.5(18–24), p = 0.007)], bronchoconstriction index [2.28(2.08–2.36) vs. 2.64(2.53–2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1β compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1β compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

2021 ◽  
Author(s):  
Kei Sato ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Yuki Matsunaga ◽  
Takashi Fujimoto ◽  
...  

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.


2018 ◽  
Vol 109 ◽  
pp. e476-e485 ◽  
Author(s):  
Jan-Karl Burkhardt ◽  
Sebastian Winklhofer ◽  
Jorn Fierstra ◽  
Susanne Wegener ◽  
Giuseppe Esposito ◽  
...  

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Songlin Yu ◽  
Samantha J Ma ◽  
David S Liebeskind ◽  
Lirong Yan ◽  
Fabien Scalzo ◽  
...  

2020 ◽  
Vol 419 ◽  
pp. 117164
Author(s):  
Jonathan Ince ◽  
Caroline Banahan ◽  
Sara Venturini ◽  
Meshal Alharbi ◽  
Poppy Turner ◽  
...  

Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3600-3608 ◽  
Author(s):  
Chunyang Wang ◽  
Rui Huang ◽  
Chao Li ◽  
Mei Lu ◽  
Martin Emanuele ◽  
...  

Background and Purpose— Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods— Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results— Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions— The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.


2020 ◽  
Vol 21 (8) ◽  
pp. 2810
Author(s):  
Xinling Song ◽  
Jianjun Zhang ◽  
Jian Li ◽  
Le Jia

The present work investigated the anti-inflammatory, antioxidant, and lung protection effects of acetylated Pleurotus geesteranus polysaccharides (AcPPS) on acute lung injury (ALI) mice. The acetylation of AcPPS was successfully shown by the peaks of 1737 cm−1 and 1249 cm−1 by FTIR. The animal experiments demonstrated that lung damage can be induced by zymosan. However, the supplementation of AcPPS had potential effects on reducing lung index, remitting inflammatory symptoms (TNF-α, IL-1β, and IL-6), inhibiting NF-κB signal pathway based on up-regulating the level of IκBα and down-regulating p-IκBα level by Western blotting and immunofluorescence assay, preventing oxidative stress (ROS, SOD, GSH-Px, CAT, T-AOC, and MDA), reducing lipid accumulation (TC, TG, LDL-C, HDL-C, and VLDL-C), and alleviating lung functions by histopathologic observation. These results demonstrated that AcPPS might be suitable for natural food for prevention or remission in ALI.


2016 ◽  
Vol 38 (2) ◽  
pp. 158-163 ◽  
Author(s):  
Serguei Semenov ◽  
Toan Huynh ◽  
Thomas Williams ◽  
Brian Nicholson ◽  
Anna Vasilenko

2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.


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