Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils
✍ Scribed by Dr Daniel M. Rosenbaum; Jason D'Amore; Josefina Llena; Susan Rybak; Adam Balkany; John A. Kessler
- Book ID
- 102707928
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 995 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0364-5134
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✦ Synopsis
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 pg 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.