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

Abstract:

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.

journal_name

Curr Opin Neurol

authors

Biegon A,Liraz-Zaltsman S,Shohami E

doi

10.1097/WCO.0000000000000612

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

687-692

issue

6

eissn

1350-7540

issn

1473-6551

pii

00019052-201812000-00005

journal_volume

31

pub_type

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