Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset

Jin, Xinchun; Liu, Jie; Yang, Yi; Liu, Ke J.; Yang, Yirong; Liu, Wenlan

doi:10.1016/j.nbd.2012.07.007

Cited by 56 publications

(47 citation statements)

References 46 publications

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“…These data may not be in accordance with a recent study on rats from Jin et al 32 who showed major BBB leakage in non-infarcted areas after 2 or 3 hours of MCAO followed by 10 minutes of reperfusion. As the experimental stroke model was quite different from ours, the results of that study suggest a different stroke severity and potentially different mechanisms than the ones occurring here to open the BBB from 4 hours after reperfusion.…”

Section: Discussioncontrasting

confidence: 95%

Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo/in Vitro Study

Kuntz

Mysiorek

Pétrault

et al. 2013

J Cereb Blood Flow Metab

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The disappointing clinical outcomes of neuroprotectants challenge the relevance of preclinical stroke models and data in defining early cerebrovascular events as potential therapeutic targets. The kinetics of blood-brain barrier (BBB) leakage after reperfusion and the link with parenchymal lesion remain debated. By using in vivo and in vitro approaches, we conducted a kinetic analysis of BBB dysfunction during early reperfusion. After 60 minutes of middle cerebral artery occlusion followed by reperfusion times up to 24 hours in mice, a non-invasive magnetic resonance imaging method, through an original sequence of diffusion-weighted imaging, determined brain water mobility in microvascular compartments (D*) apart from parenchymal compartments (apparent diffusion coefficient). An increase in D* found at 4 hours post reperfusion concurred with the onset of both Evans blue/Dextran extravasations and in vitro BBB opening under oxygen-glucose deprivation and reoxygenation (R). The BBB leakage coincided with an emerging cell death in brain tissue as well as in activated glial cells in vitro. The co-culture of BBB endothelial and glial cells evidenced a recovery of endothelium tightness when glial cells were absent or non-injured during R. Preserving the ischemic brain parenchymal cells within 4 hours of reperfusion may improve therapeutic strategies for cerebrovascular protection against stroke.

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Section: Discussioncontrasting

confidence: 95%

Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo/in Vitro Study

Kuntz

Mysiorek

Pétrault

et al. 2013

J Cereb Blood Flow Metab

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“…However, in both these genotypes fibrin deposition within the infarct zone (indicative of altered blood vessel permeability) remained intravascular, compared with extravascular fibrin reactivity in PAI-1 À / À mice. 121 These findings indicate the involvement of endogenous plasmin in neuronal death, but not in BBB alteration during stroke (consistent with the notion that BBB disruption and neurotoxicity are distinguishable events in the rodent [75][76][77], in contrast to endogenous tPA, which participates in both.…”

Section: Experiments In Plasminogen Knockout Micesupporting

confidence: 80%

Plasmin-Dependent Modulation of the Blood–Brain Barrier: A Major Consideration during tPA-Induced Thrombolysis?

Niego

Medcalf

2014

J Cereb Blood Flow Metab

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Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood-brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process.

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“…Pretreatment with MMP inhibitor GM6001 significantly reduced dextran leakage induced by 2 and 3 h MCAO. (Jin et al, 2012) Further studies demonstrated that hypoxia-induced secretion of MMP-2 in ECs mediated occludin degradation, and caveolin-1-mediated claudin-5 redistribution. (Liu et al, 2012) In reperfusion model of rat, treatment with normobaric hyperoxia (NBO) initiated 5 min after MCAO onset for one h, decreases degradation of TJPs-mediated by MMP-2 and -9 and attenuates disruption of the BBB in reperfusion injury of 48 h.(Jin et al, 2013; Liu et al, 2009) When hyperoxia is used with tPA, there is reduction in hemorrhagic complications from tPA, probably because of the protection of the BBB.…”

Section: Introductionmentioning

confidence: 99%

“…(Jin et al, 2012) Animal and human studies found that thrombolysis-associated cerebral hemorrhage occurred in the brain regions where the BBB was compromised. (Bang et al, 2007; Hjort et al, 2008; Hom et al, 2011; Kassner et al, 2009; Sun et al, 2010; Wu et al, 2009) These studies suggest that loss of BBB integrity during cerebral ischemia may predispose ischemic brain tissue to bleeding during reperfusion with thrombolysis.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases as therapeutic targets for stroke

2015

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Matrix metalloproteinases (MMPs) are important in injury and recovery in ischemic injury. They are proteolytic enzymes that degrade all components of the extracellular matrix (ECM). They are secreted in a latent form, protecting the cell from damage, but once activated induce injury prior to rapid inactivation by four tissue inhibitors to metalloproteinases (TIMPs). Normally the constitutive enzymes, MMP-2 and membrane type MMP (MMP-14), are activated in a spatially specific manner and act close to the site of activation, while the inducible enzymes, MMP-3 and MMP-9, become active through the action of free radicals and other enzymes during neuroinflammation. Because of the complex nature of the interactions with tissues during development, injury and repair, the MMPs have multiple roles, participating in the injury process in the early stages and contributing to recovery during the later stages. This dual role complicates the planning of treatment strategies.

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Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset

Cited by 56 publications

References 46 publications

Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo/in Vitro Study

Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo/in Vitro Study

Plasmin-Dependent Modulation of the Blood–Brain Barrier: A Major Consideration during tPA-Induced Thrombolysis?

Matrix metalloproteinases as therapeutic targets for stroke

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