Effects of Memantine on Nitric Oxide Production and Hydroxyl Radical Metabolism during Cerebral Ischemia and Reperfusion in Mice.

Abstract

BACKGROUND:

The purpose of this study was to investigate the effects of memantine on brain ischemia. Because we can measure nitric oxide (NO) production and hydroxyl radical metabolism continuously, we investigated the effect of memantine on NO production and hydroxyl radical metabolism in cerebral ischemia and reperfusion.

METHODS:

Memantine (25 µmol/kg) was administered intraperitoneally to 6 C57BL/6 mice 30 minutes before ischemia. Seven additional mice received no injection (controls). NO production and hydroxyl radical metabolism were continuously monitored using bilateral striatal microdialysis in vivo. Hydroxyl radical formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by occluding the common carotid artery bilaterally for 10 minutes. Levels of the NO metabolites nitrite (NO2-) and nitrate (NO3-) were determined using the Griess reaction. Survival rates of hippocampal CA1 neurons were calculated and 8-hydroxydeoxyguanosine (8-OHdG)-immunopositive cells were counted to evaluate the oxidative stress in hippocampal CA1 neurons 72 hours after the start of reperfusion.

RESULTS:

The regional cerebral blood flow was significantly higher in the memantine group than in the control group after reperfusion. Furthermore, the level of 2,3-dihydroxybenzoic acid was significantly lower in the memantine group than in the control group during ischemia and reperfusion. Levels of NO2- and NO3- did not differ significantly between the 2 groups. Although survival rates in the CA1 did not differ significantly, there were fewer 8-OHdG-immunopositive cells in animals that had received memantine than in control animals.

CONCLUSIONS:

These data suggest that memantine exerts partially neuroprotective effects against cerebral ischemic injury.

• Authors: Ai Tanaka, Yasuo Ito, Hitoshi Kawasaki, Chika Kitabayashi, Ryoji Nishioka, Masamizu Yamazato, Keisuke Ishizawa, Toshinori Nagai, Makiko Hirayama, Kazushi Takahashi, Toshimasa Yamamoto, Nobuo Araki
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 27 Issue 6 Pg. 1609-1615 (Jun 2018) ISSN: 1532-8511 [Electronic] United States
• PMID: 29426680 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Biomarkers
• Neuroprotective Agents
• Nitric Oxide
• Hydroxyl Radical
• Memantine

Topics

• Animals
• Antioxidants (pharmacology)
• Biomarkers (metabolism)
• Blood Flow Velocity
• Brain Ischemia (metabolism, pathology, physiopathology, prevention & control)
• CA1 Region, Hippocampal (blood supply, drug effects, metabolism, pathology)
• Cerebrovascular Circulation (drug effects)
• Cytoprotection
• Disease Models, Animal
• Hydroxyl Radical (metabolism)
• Memantine (pharmacology)
• Mice, Inbred C57BL
• Microdialysis
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Time Factors