AUTHOR=Albrecht Carolin , Harms Christoph , Kreye Jakob , Endres Matthias , Mueller Susanne , Boehm-Sturm Philipp , Koch Stefan Paul , Freyer Dorette , Prüss Harald , Knauss Samuel 

TITLE=Intraperitoneal administration of NMDA-Subunit NR1-receptor antibodies does not improve long-term outcome in a murine MCAo-stroke model

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1614924

DOI=10.3389/fnins.2025.1614924

ISSN=1662-453X

ABSTRACT=Ischemic stroke is a major cause of disability worldwide, and current treatment is largely limited to thrombolytics. Therefore, additional therapeutic strategies are warranted. Previous evidence suggests that NMDA receptor antibodies targeting specific subunits may reduce excitotoxicity and lesion size. This study evaluates the effects of a specific NMDAR-NR1 antibody in both in vitro and in vivo models of ischemic stroke. Neuronal cultures were treated with NMDAR-NR1-AB, a control antibody (mGO-AB) or phosphate-buffered saline followed by NMDA exposure or oxygen-glucose deprivation (OGD). Cell death was measured by lactate dehydrogenase assay. NMDA and OGD significantly increased cell death, but NMDAR-NR1-AB did not exert neuroprotective effects in vitro. In vivo, C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAo) for 45 min and treated intraperitoneally with NMDAR-NR1-AB or mGO-AB. Lesion size and neurobehavioral outcomes were assessed at 24 and 72 h and 28 days after MCAo. No differences in lesion sizes or long-term neuroprotective effects were evident at 24 h and 28 days post-MCAo. These findings underscore both the potential and limitations of targeting NMDAR-mediated excitotoxicity in ischemic stroke therapy and highlight the need for further research into the long-term efficacy of NMDAR-NR1-AB.