Stimulation of N-methyl-D-aspartate receptors by exogenous and endogenous ligands improves outcome of brain injury

Anat Biegon, Sigal Liraz-Zaltsman, Esther Shohami*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


Purpose of review The failure of N-methyl-D-aspartate receptor (NMDAR) antagonists as a treatment for human traumatic brain injury (TBI) and stroke, along with preclinical findings of a persistent hypofunctional state of these receptors after brain injury, resulted in a new focus on NMDAR agonists, specifically those acting via the glycine site of the NMDAR. This article reviews the recent literature on positive modulators of the glycine site as a new modality for improving cognitive function in central nervous system pathology, including traumatic and ischemic brain injuries, neuroinflammation, and neuropsychiatric disorders. Recent findings A sustained cognitive decline and NMDAR downregulation were reported in rodent models of TBI, developmental TBI, stroke, and lipopolysaccharide-induced neuroinflammation. Activation of the glycine/ serine site by D-cycloserine (DCS) or D-serine ameliorated these cognitive deficits. Recent reviews and reports on the use of DCS and D-serine to modify memory function in a wide range of psychiatric conditions are generally positive. Summary Taken together, the preclinical and clinical studies provide new, additional support for the notion that activation of the glycine/serine site should be considered a novel therapeutic approach to cognitive impairments. Specifically, as DCS is an approved drug, its translation into clinical practice should be advocated.

Original languageAmerican English
Pages (from-to)687-692
Number of pages6
JournalCurrent Opinion in Neurology
Issue number6
StatePublished - 2018

Bibliographical note

Funding Information:
Part of this work was supported by a grant from the Dr Miriam and Sheldon Adelson Foundation (AMRF) to E.S.

Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.


  • Brain injury
  • D-cycloserine
  • Glycine/serine binding site
  • N-methyl-D-aspartate receptor


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