Very Mild Hypothermia (35°C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse

2015 ◽  
Vol 5 (4) ◽  
pp. 203-208 ◽  
Author(s):  
Brian K. Cechmanek ◽  
Ursula I. Tuor ◽  
David Rushforth ◽  
Philip A. Barber
2018 ◽  
Author(s):  
Ana I Casas ◽  
Pamela WM Kleikers ◽  
Eva Geuss ◽  
Friederike Langhauser ◽  
Javier Egea ◽  
...  

AbstractIschemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal of the occlusion being the only therapeutic options. Reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain-barrier. Its mechanism, however, is unknown. Here we identify type 5 NADPH oxidase (NOX5), a calcium-activated, reactive oxygen species (ROS)-forming enzyme as missing link. Using a humanised knock-in mouse model and in vitro in organotypic cultures, we find re-oxygenation or calcium overload to increase brain ROS levels in a NOX5-dependent manner. In vivo, post-ischemic ROS formation, infarct volume and functional outcomes were worsened in NOX5 knock-in mice. Of clinical and therapeutic relevance, in a human blood-barrier model pharmacological NOX inhibition also prevented acute re-oxygenation induced leakage. Our data therefore identify NOX5 as sufficient to induce acute post-reperfusion calcium-dependent blood-brain-barrier breakdown. We suggest urgent clinical validation by conducting protective post-stroke re-canalisation in the presence of a NOX inhibitor.


2020 ◽  
Vol 18 (9) ◽  
pp. 713-722 ◽  
Author(s):  
Ganji Hong ◽  
Ying Yan ◽  
Yali Zhong ◽  
Jianer Chen ◽  
Fei Tong ◽  
...  

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.


2014 ◽  
Vol 229 (3) ◽  
pp. 415-422 ◽  
Author(s):  
Edilene Siqueira Soares ◽  
Monique Culturato Padilha Mendonça ◽  
Silvia Pierre Irazusta ◽  
Andressa Coope ◽  
Leila Miguel Stávale ◽  
...  

2018 ◽  
Vol 14 (12) ◽  
pp. 1640-1650 ◽  
Author(s):  
Gene L. Bowman ◽  
Loïc Dayon ◽  
Richard Kirkland ◽  
Jérôme Wojcik ◽  
Gwendoline Peyratout ◽  
...  

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