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Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils
Author(s) -
Rosenbaum Daniel M.,
D'Amore Jason,
Llena Josefina,
Rybak Susan,
Balkany Adam,
Kessler John A.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410430515
Subject(s) - aurintricarboxylic acid , apoptosis , ischemia , transient (computer programming) , medicine , pharmacology , anesthesia , chemistry , cardiology , programmed cell death , biochemistry , computer science , operating system
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. Transien ischemia was induced in gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four micrograms of ATA was administered intraventricularly I 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 μg 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.