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: Rashna Balsara, Alexander Dang, Deborah L Donahue, Tiffany Snow, Francis J Castellino
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0122840 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25822337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Conotoxins
• MAP2 protein, rat
• Microtubule-Associated Proteins
• NR2B NMDA receptor
• Neuroprotective Agents
• Protein Subunits
• Receptors, N-Methyl-D-Aspartate
• conotoxin GV

Topics

• Animals
• Brain (drug effects, metabolism, pathology)
• Brain Infarction (complications, drug therapy, metabolism, pathology)
• Conotoxins (pharmacology, therapeutic use)
• Disease Models, Animal
• Male
• Microtubule-Associated Proteins (metabolism)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Protein Subunits (metabolism)
• Protein Transport (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Reperfusion Injury (complications)
• Time Factors
• Treatment Outcome