LncRNA Snhg8 attenuates microglial inflammation response and blood–brain barrier damage in ischemic stroke through regulating miR‐425‐5p mediated SIRT1/NF‐κB signaling

2021 ◽  
Author(s):  
Jianan Tian ◽  
Yihang Liu ◽  
Zhenqi Wang ◽  
Siqi Zhang ◽  
Yue Yang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Inflammation Response ◽  
Blood Brain ◽  
Blood Brain Barrier Damage ◽  
Microglial Inflammation

scholarly journals Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 4082-4092 ◽  
Author(s):  
Friederike Langhauser ◽  
Eva Göb ◽  
Peter Kraft ◽  
Christian Geis ◽  
Joachim Schmitt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Thrombus Formation ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Edema Formation ◽  
Kinin System ◽  
Local Inflammatory Response ◽  
Blood Brain ◽  
Blood Brain Barrier Damage

Abstract Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng−/− mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng−/− mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases.

scholarly journals Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15106 ◽  
Author(s):  
Peter Kraft ◽  
Peter Michael Benz ◽  
Madeleine Austinat ◽  
Marc Elmar Brede ◽  
Kai Schuh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain ◽  
Blood Brain Barrier Damage

scholarly journals Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function

Stroke ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 478-486 ◽  
Author(s):  
Michael Bieber ◽  
Michael K. Schuhmann ◽  
Julia Volz ◽  
Gangasani Jagadeesh Kumar ◽  
Jayathirtha Rao Vaidya ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Platelet Function ◽  
Focal Cerebral Ischemia ◽  
Brain Barrier ◽  
Local Inflammatory Response ◽  
Blood Brain ◽  
Blood Brain Barrier Damage

Background and Purpose— Acetylsalicylic acid and clopidogrel are the 2 main antithrombotic drugs for secondary prevention in patients with ischemic stroke (IS) without indication for anticoagulation. Because of their limited efficacy and potential side effects, novel antiplatelet agents are urgently needed. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, protected from IS in clinical studies comprising mainly Asian populations. Nevertheless, the detailed mechanistic role of PDE-3 inhibitors in IS pathophysiology is hardly understood. In this project, we analyzed the efficacy and pathophysiologic mechanisms of a novel and only recently described PDE-3 inhibitor (substance V) in a mouse model of focal cerebral ischemia. Methods— Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in 6- to 8-week-old male C57Bl/6 wild-type mice receiving substance V or vehicle 1 hour after ischemia induction. Infarct volumes and functional outcomes were assessed between day 1 and day 7, and findings were validated by magnetic resonance imaging. Blood-brain barrier damage, as well as the extent of local inflammatory response and cell death, was determined. Results— Inhibition of PDE-3 by pharmacological blockade with substance V significantly reduced infarct volumes and improved neurological outcome on day 1 and 7 after experimental cerebral ischemia. Reduced blood-brain barrier damage, attenuated brain tissue inflammation, and decreased local cell death could be identified as potential mechanisms. PDE-3 inhibitor treatment did neither increase the number of intracerebral hemorrhages nor affect platelet function. Conclusions— The novel PDE-3 inhibitor substance V protected mice from IS independent from platelet function. Pharmaceutical inactivation of PDE-3 might become a promising therapeutic approach to combat IS via inhibition of thromboinflammatory mechanisms and stabilization of the blood-brain barrier.

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