title: Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils.
abstract: The goal of this study was to determine whether aurintricarboxylic acid (ATA), an endonuclease inhibitor known to inhibit apoptosis, could ameliorate cell damage in a gerbil model of transient ischemia. Transient ischemia was induced in gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four micrograms of ATA was administered intraventricularly 1 hour before ischemia, and the brains were assessed histologically 1 week later to quantitate cell loss in the vulnerable CA-1 subsector of the hippocampus. In a separate set of experiments, 4 microg of ATA was administered intraventricularly 1 hour before ischemia and the brains were assessed for evidence of DNA fragmentation by the TUNEL method. There was only a 16% cell loss compared with nonischemic controls in animals pretreated with ATA that was significantly less (p < 0.05) than the 48% cell loss in animals pretreated with saline alone. TUNEL-positive cells were first evident at 3 days and were still present at 7 days subsequent to ischemia. Maximal staining occurred at 4 days. Pretreatment with ATA virtually eliminated TUNEL staining at 4 days. These results support the hypothesis that the delayed cell death secondary to transient ischemia is, in part, apoptotic. Furthermore, ATA afforded significant neuronal protection and prevented DNA fragmentation.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Rosenbaum
authors.forename: J
authors.initials: J
authors.lastname: D'Amore
authors.forename: J
authors.initials: J
authors.lastname: Llena
authors.forename: S
authors.initials: S
authors.lastname: Rybak
authors.forename: A
authors.initials: A
authors.lastname: Balkany
authors.forename: J A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001710:Biotin; D001831:Body Temperature; D002452:Cell Count; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D004720:Endonucleases / Q000037:antagonists & inhibitors; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D003856:Deoxyuracil Nucleotides; D018696:Neuroprotective Agents; D001312:Aurintricarboxylic Acid; D001710:Biotin; D004720:Endonucleases