Stimulation of N-methyl-D-aspartate receptors by exogenous and endogenous ligands improves outcome of brain injury.
Curr Opin Neurol
; 31(6): 687-692, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30382950
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de N-Metil-D-Aspartato
/
Lesões Encefálicas Traumáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos