title: Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury.
abstract: The postsynaptic density-95 inhibitor NA-1 uncouples NMDA glutamate receptors from downstream neurotoxic signaling pathways without affecting normal glutamate receptor function. NA-1 attenuates NMDA receptor-mediated neuronal cell death after stroke in multiple models and species. However, its efficacy in providing neuroprotection in models of neonatal hypoxic-ischemic brain injury has not yet been tested. In this study, a modified version of the Rice-Vannucci method for the induction of neonatal hypoxic-ischemic brain injury was performed on postnatal day 7 mouse pups. Animals received a single dose of NA-1 intraperitoneally either before or after right common carotid artery occlusion. All experiments were performed in a blinded manner. Infarct volumes were measured 1 and 7 days after the injury, while behavioral tests were conducted 1, 3, and 7 days after injury. Administration of NA-1 before right common carotid artery occlusion or immediately after ischemia significantly reduced infarct volume and improved neurobehavioral outcomes 1, 3, and 7 days post-injury. The neuroprotection and improvement in neurobehavioral outcomes conferred by NA-1 in this mouse neonatal hypoxic-ischemic injury model imply that NA-1 will be effective in reducing neonatal stroke damage and thus could potentially serve as a therapeutic drug for prevention or treatment of neonatal stroke.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Ai-Jiao
authors.initials: AJ
authors.lastname: Xiao
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 1A8.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Turlova
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barszczyk
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Christopher L F
authors.initials: CLF
authors.lastname: Sun
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 1A8.
authors.forename: Michael
authors.initials: M
authors.lastname: Tymianski
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8. zp.feng@utoronto.ca.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8. hss.sun@utoronto.ca.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8. hss.sun@utoronto.ca.|Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 1A8. hss.sun@utoronto.ca.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 1A8. hss.sun@utoronto.ca.
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000076122:Disks Large Homolog 4 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000076122:Disks Large Homolog 4 Protein; D018696:Neuroprotective Agents; D010455:Peptides; C542597:Tat-NR2B9c; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: In vivo; Neonatal hypoxic-ischemic brain injury; Neonatal stroke; Neuroprotection; PSD-95