Skip to Main content Skip to Navigation
Theses

NMDA receptor of the blood brain barrier : mechanism of action and interaction with tPA

Abstract : Neuroinflammation is a common denominator of several central nervous system disorders. Inflammatory reactions are often mediated by several signaling pathways which lead to the opening of the blood brain barrier. Tissue plasminogen activator (tPA) is a serine protease induces opening of the blood brain barrier. In recent years, it has also been shown that NMDA receptors located in endothelial cells can play a crucial role in propagation of inflammatory reaction. My doctoral study focused on the finding the underlying mechanisms of action(s) by which NMDA receptor mediates tPA induced opening of the blood brain barrier. In our first study we show that endothelial NMDA receptors are potential therapeutic targets to prevent EAE mediated immune cell infiltration and inflammation. We show that NMDA receptor specific mouse monoclonal antibody Glunomab could prevent the brain spinal cord barrier from inflammatory damage. We also show that NMDA receptors are expressed in close association of tight junction proteins in cerebral endothelial cells. In our second study, we show for the first time that, neuroendothelial NMDA receptors can exhibit metabotropic mode of action during inflammation. We also highlight that these receptors are indeed GluN3A expressing non-conventional NMDA receptors. In addition, we report that tPA accelerates the opening of blood brain barrier in presence of an uncommon agonist glycine by RhoA activation dependent mechanism.My project results provide a nouvelle insight for the role of metabotropic NMDA receptors in cerebral endothelial cells. In addition it also provides more precise details of blood brain barrier opening mediated by tissue plasminogen activator.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-01806346
Contributor : Abes Star :  Contact
Submitted on : Saturday, June 2, 2018 - 1:14:23 AM
Last modification on : Wednesday, November 27, 2019 - 3:06:34 AM
Long-term archiving on: : Monday, September 3, 2018 - 3:49:01 PM

File

2017-MEHRA-ANUPRIYA-VO.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01806346, version 1

Citation

Anupriya Mehra. NMDA receptor of the blood brain barrier : mechanism of action and interaction with tPA. Biochemistry, Molecular Biology. Normandie Université, 2017. English. ⟨NNT : 2017NORMC404⟩. ⟨tel-01806346⟩

Share

Metrics

Record views

280

Files downloads

191