Glycine-induced NMDA receptor internalization provides neuroprotection and preserves vasculature following ischemic stroke

• DOI: 10.1016/j.isci.2021.103539
• Publication Date: 2021-12-03T04:45:04Z
• Authors: Julia Cappelli; Pamela Khacho; Boyang Wang; Alexandra Sokolovski; Wafae Bakkar; Sophie Raymond; Nina Ahlskog; Julian Pitney; Junzheng Wu; Prakash Chudalayandi; Adrian Y.C. Wong; Richard Bergeron
• Keywords: Stroke; Nimodipine; Internalization

Ischemic stroke is the second leading cause of death worldwide. Following an ischemic event, neuronal triggered by uncontrolled glutamate release to overactivation sensitive N-methyl-d-aspartate receptor (NMDAR). For gating, NMDARs require not only binding glutamate, but also glycine or a glycine-like compound as co-agonist. Low doses enhance NMDAR function, whereas high trigger glycine-induced internalization (GINI) in vitro. Here, we report that following vivo, GINI occurs and provides neuroprotection presence GlyT1 antagonist (GlyT1-A). Mice pretreated with GlyT1-A, which increases synaptic levels, exhibited smaller volume, reduced cell death, minimized behavioral deficits induction either photothrombosis endothelin-1. Moreover, show evidence conditions, GlyT1-As preserve vasculature peri-infarct area. Therefore, could be new target for treatment stroke.