Cerebral Edema Formation and Blood-Brain Barrier Impairment by Intraventricular Collagenase Infusion

Author(s):  
J. Gazendam ◽  
H. J. Houthoff ◽  
S. Huitema ◽  
K. G. Go
2021 ◽  
Vol 15 ◽  
Author(s):  
Sichao Chen ◽  
Linqian Shao ◽  
Li Ma

Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion and may also result in transtentorial herniation. As a physical and biochemical barrier between the peripheral circulation and the central nervous system (CNS), the blood–brain barrier (BBB) plays a vital role in maintaining the stable microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the dysfunction of the BBB results in increased paracellular permeability, directly contributing to the extravasation of blood components into the brain and causing cerebral vasogenic edema. Recent studies have led to the discovery of the glymphatic system and meningeal lymphatic vessels, which provide a channel for cerebrospinal fluid (CSF) to enter the brain and drain to nearby lymph nodes and communicate with the peripheral immune system, modulating immune surveillance and brain responses. A deeper understanding of the function of the cerebral lymphatic system calls into question the known mechanisms of cerebral edema after stroke. In this review, we first discuss how BBB disruption after stroke can cause or contribute to cerebral edema from the perspective of molecular and cellular pathophysiology. Finally, we discuss how the cerebral lymphatic system participates in the formation of cerebral edema after stroke and summarize the pathophysiological process of cerebral edema formation after stroke from the two directions of the BBB and cerebral lymphatic system.


2015 ◽  
Vol 266 ◽  
pp. 99-111 ◽  
Author(s):  
Reiner Kunze ◽  
Andrés Urrutia ◽  
Angelika Hoffmann ◽  
Hui Liu ◽  
Xavier Helluy ◽  
...  

2018 ◽  
Vol 39 (9) ◽  
pp. 1678-1692 ◽  
Author(s):  
Natalie Y Yuen ◽  
Olga V Chechneva ◽  
Yi-Je Chen ◽  
Yi-Chen Tsai ◽  
Logan K Little ◽  
...  

Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood–brain barrier (BBB) Na–K–Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke. Cerebral microvascular endothelial cell (CMEC) NKCC and NHE abundances and activities were determined by Western blot, radioisotopic flux and microspectrofluorometric methods. Cerebral edema and Na in rats subjected to middle cerebral artery occlusion (MCAO) were assessed by nuclear magnetic resonance methods. Hyperglycemia exposures of 1-7d significantly increased CMEC NKCC and NHE abundance and activity. Subsequent exposure to ischemic factors caused more robust increases in NKCC and NHE activities than in normoglycemic CMEC. MCAO-induced edema and brain Na uptake were greater in hyperglycemic rats. Intravenous bumetanide and HOE-642 significantly attenuated edema, brain Na uptake and ischemic injury. Our findings provide evidence that BBB NKCC and NHE contribute to increased edema in hyperglycemic stroke, suggesting that these Na transporters are promising therapeutic targets for reducing damage in diabetic stroke.


Author(s):  
A. Lorris Betz ◽  
Steven R. Ennis ◽  
Xiao-dan Ren ◽  
Gerald P. Schielke ◽  
Richard F. Keep

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 4082-4092 ◽  
Author(s):  
Friederike Langhauser ◽  
Eva Göb ◽  
Peter Kraft ◽  
Christian Geis ◽  
Joachim Schmitt ◽  
...  

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.


Brain Edema ◽  
2017 ◽  
pp. 129-149 ◽  
Author(s):  
Martha E. O’Donnell ◽  
Heike Wulff ◽  
Yi-Je Chen

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