title: Amiloride but not memantine reduces neurodegeneration, seizures and myoclonic jerks in rats with cardiac arrest-induced global cerebral hypoxia and reperfusion.
abstract: It has been reported that both activation of N-methyl-D-aspartate receptors and acid-sensing ion channels during cerebral ischemic insult contributed to brain injury. But which of these two molecular targets plays a more pivotal role in hypoxia-induced brain injury during ischemia is not known. In this study, the neuroprotective effects of an acid-sensing cation channel blocker and an N-methyl-D-aspartate receptor blocker were evaluated in a rat model of cardiac arrest-induced cerebral hypoxia. We found that intracisternal injection of amiloride, an acid-sensing ion channel blocker, dose-dependently reduced cerebral hypoxia-induced neurodegeneration, seizures, and audiogenic myoclonic jerks. In contrast, intracisternal injection of memantine, a selective uncompetitive N-methyl-D-aspartate receptor blocker, had no significant effect on cerebral hypoxia-induced neurodegeneration, seizure and audiogenic myoclonic jerks. Intracisternal injection of zoniporide, a specific sodium-hydrogen exchanger inhibitor, before cardiac arrest-induced cerebral hypoxia, also did not reduce cerebral hypoxia-induced neurodegeneration, seizures and myoclonic jerks. These results suggest that acid-sensing ion channels play a more pivotal role than N-methyl-D-aspartate receptors in mediating cerebral hypoxia-induced brain injury during ischemic insult.
authors.affiliation: The Parkinson's and Movement Disorder Research Laboratory, Long Beach Memorial Medical Center, Long Beach, California, United States of America. kktai@uci.edu
authors.forename: Kwok Keung
authors.initials: KK
authors.lastname: Tai
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Truong
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006323:Heart Arrest / Q000150:complications*; D002534:Hypoxia, Brain / Q000150:complications / Q000209:etiology*; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D009207:Myoclonus / Q000150:complications / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000209:etiology*; D012640:Seizures / Q000150:complications / Q000188:drug therapy*
chemical_list: D062565:Acid Sensing Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D000584:Amiloride; D008559:Memantine