Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis.

@article{Macrez2016NeuroendothelialNR,
  title={Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis.},
  author={Richard Macrez and Mar{\'i}a Cristina Ortega and Isabelle Bardou and Anupriya Mehra and Antoine P. Fournier and Susanne M. A. van der Pol and Benoit Haelewyn and Eric Maubert and Flavie Lesept and Arnaud Chevilley and Fernando de Castro and Helga E. de Vries and Denis Vivien and Diego Clemente and Fabian Docagne},
  journal={Brain : a journal of neurology},
  year={2016},
  volume={139 Pt 9},
  pages={
          2406-19
        }
}
Multiple sclerosis is among the most common causes of neurological disability in young adults. Here we provide the preclinical proof of concept of the benefit of a novel strategy of treatment for multiple sclerosis targeting neuroendothelial N-methyl-D-aspartate glutamate receptors. We designed a monoclonal antibody against N-methyl-D-aspartate receptors, which targets a regulatory site of the GluN1 subunit of N-methyl-D-aspartate receptor sensitive to the protease tissue plasminogen activator… Expand
Autoimmune encephalitis mediated by B-cell response against N-methyl-d-aspartate receptor.
TLDR
It is demonstrated that the B-cell response can lead to an autoimmune reaction against NMDAR that drives encephalitis-like behavioural impairments, and this study provides a relevant platform for dissecting encephalitogenic mechanisms in an animal model, and enables the testing of therapeutic strategies targeting the immune system in anti-NMDAREncephalitis mice. Expand
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Possible reasons for the differential effects of GluN1 antibodies on NMDAR physiology that could contribute to these phenotypes are discussed. Expand
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Understanding of the mechanisms underlying glutamate toxicity in multiple sclerosis could help in the development of new approaches for diagnosis, treatment, and follow-up in patients with this debilitating disease. Expand
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Reports on the mechanisms leading to increases in the concentration of the neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of the disease are presented. Expand
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It is proposed that endothelial NMDAR dysfunction can be a primary cause of neurovascular abnormalities in schizophrenia, and functional MRI studies using BOLD signal as a proxy for neuron activity should be considered in a new light if neurov vascular coupling is impaired in schizophrenia. Expand
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The biological characteristics and pleiotropic functions of tPA in the brain are summarized and possible hypotheses about why and how endogenous tPA mediates ischemic neuronal death and survival are focused on. Expand
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The authors describe how NMDARs expressed on endothelial cells regulate blood–brain barrier function via myosin light chain phosphorylation and increase in permeability and report that these non-neuronal N MDARs display distinct structural, functional, and pharmacological features than their neuronal counterparts. Expand
Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors
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TLDR
The tPA present in the blood circulation is capable of potentiating the cerebral blood flow increase induced by the activation of the mouse somatosensorial cortex, and that this effect is mediated by a tPA-dependent activation of NMDAR expressed at the luminal part of endothelial cells of arteries. Expand
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