Inhibition of poly (ADP-ribose) polymerase and caspase-3, but not caspase-1, prevents apoptosis and improves spatial memory of rats with twice-repeated cerebral ischemia

Izzettin Hatip-Al-Khatib, Katsunori Iwasaki, Eun Hee Chung, Nobuaki Egashira, Kenichi Mishima, Michihiro Fujiwara

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Abstract

The effect of inhibition of PARP [(poly (ADP-ribose) polymerase], caspase-3 and caspase-1 on twice-repeated ischemia-induced apoptosis and memory impairment were examined. The twicerepeated ischemia was induced by four-vessel occlusion method in which a 10 min ischemic episode was repeated once after 60 min. The spatial memory was assessed using 8-arm radial maze. The results of this study showed that the repeated ischemia impaired memory and induced apoptosis in hippocampus CA1 field after 7 days. Moreover, 3-aminobezamide (10 mg/kg i.v.), a PARP inhibitor, and Ac-DEVD-CHO (8.4 μg/5 μL i.c.v., bilaterally), a caspase-3 inhibitor, decreased apoptosis by 45% and 58% respectively. Both drugs reduced the error choices, but 3-aminobezamide additionally increased the correct choices and improved the memory when either drug was injected immediately after the ischemic insult. The results also showed that inhibition of interleukin-1β-converting enzyme, ICE (caspase-1) by Z-ASP-DCB-CH2 (100 μg/kg i.c.v., bilaterally) neither decreased apoptosis (13% reduction) nor improved memory of the ischemic rats. These results suggest that direct inhibition of PARP and caspase-3, but not of caspase-1, prevents apoptosis and improves spatial memory impaired by repeated ischemia.

Original languageEnglish
Pages (from-to)1967-1978
Number of pages12
JournalLife Sciences
Volume75
Issue number16
DOIs
Publication statusPublished - Sep 3 2004
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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