Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin

Garraud, Marie; Khacef, Kahina; Vion, Anne-Clémence; Leconte, Claire; Yin, Min; Renard, Jean–Marie; Marchand-Leroux, Catherine; Boulanger, Chantal M.; Margaill, Isabelle

doi:10.1016/j.jns.2016.09.026

Cited by 6 publications

(2 citation statements)

References 51 publications

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“…Similar to 67-kDa LR neutralization, recombinant tissue plasminogen activator (r-tPA) induces BBB disruption, and subsequently results in vasogenic edema (Copin et al, 2011), which is mitigated by p38 MAPK inhibitor (Garraud et al, 2016). Rosuvastatin (a lipid-lowering agent) also ameliorates r-tPA-induced BBB damage by reducing the activities of JNK and p38 MAPK (Lu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Park

Choi

Kong

et al. 2019

Front. Cell. Neurosci.

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Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis.

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Section: Discussionmentioning

confidence: 99%

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Park

Choi

Kong

et al. 2019

Front. Cell. Neurosci.

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“…(Jickling et al, 2014; Wang et al, 2015a; Wang et al, 2004). Further study showed that rt-PA through plasmin enhances endothelial microparticle release, which has an impact on growth and morphology of cerebral endothelial cells (Garraud et al, 2016). Microparticles are membrane vesicles that are produced by cell activation or apoptosis and contribute to inflammation, thrombosis, and angiogenesis.…”

Section: Recently Identified Therapeutic Aims and Therapiesmentioning

confidence: 99%

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Shekhar

Cunningham

Pabbidi

et al. 2018

European Journal of Pharmacology

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Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment. These include blocking harmful inflammatory signaling in endothelial cells, microglia/macrophages, or Th17/γδ T cells with biologics, third generation epoxyeicosatrienoic acid (EET) analogs with extended half-life, and miRNA antagomirs. Complementary beneficial pathways may be enhanced by miRNA mimetics or hyperbaric oxygenation. These immunomodulatory approaches could be used to greatly expand the therapeutic window for thrombolytic treatment with tissue plasminogen activator (t-PA). Moreover, nanoparticle technology allows for the selective targeting of endothelial cells for delivery of DNA/RNA oligonucleotides and neuroprotective drugs. In addition, although likely detrimental to the progression of ischemic stroke by inducing inflammation, oxidative stress, and neuronal cell death, 20-HETE may also reduce susceptibility of onset of ischemic stroke by maintaining autoregulation of cerebral blood flow. Although the interaction between inflammation and stroke is multifaceted, a better understanding of the mechanisms behind the pro-inflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.

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Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target Intervention

Yan

Zhou

et al. 2018

J Mol Neurosci

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Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin

Cited by 6 publications

References 51 publications

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target Intervention

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