title: Conantokin-G attenuates detrimental effects of NMDAR hyperactivity in an ischemic rat model of stroke.
abstract: The neuroprotective activity of conantokin-G (con-G), a naturally occurring antagonist of N-methyl-D-aspartate receptors (NMDAR), was neurologically and histologically compared in the core and peri-infarct regions after ischemia/reperfusion brain injury in male Sprague-Dawley rats. The contralateral regions served as robust internal controls. Intrathecal injection of con-G, post-middle carotid artery occlusion (MCAO), caused a dramatic decrease in brain infarct size and swelling at 4 hr, compared to 26 hr, and significant recovery of neurological deficits was observed at 26 hr. Administration of con-G facilitated neuronal recovery in the peri-infarct regions as observed by decreased neurodegeneration and diminished calcium microdeposits at 4 hr and 26 hr. Intact Microtubule Associated Protein (MAP2) staining and neuronal cytoarchitecture was observed in the peri-infarct regions of con-G treated rats at both timepoints. Con-G restored localization of GluN1 and GluN2B subunits in the neuronal soma, but not that of GluN2A, which was perinuclear in the peri-infarct regions at 4 hr and 26 hr. This suggests that molecular targeting of the GluN2B subunit has potential for reducing detrimental consequences of ischemia. Overall, the data demonstrated that stroke-induced NMDAR excitoxicity is ameliorated by con-G-mediated repair of neurological and neuroarchitectural deficits, as well as by reconstituting neuronal localization of GluN1 and GluN2B subunits in the peri-infarct region of the stroked brain.
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, United States of America; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, United States of America.
authors.forename: Rashna
authors.initials: R
authors.lastname: Balsara
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dang
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, United States of America.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Donahue
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, United States of America; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, United States of America.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Snow
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, United States of America; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, United States of America.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020916:Conotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020916:Conotoxins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C055407:conotoxin GV
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