Effect of Ibudilast on Learning and Memory in Rats with Ligation of Bilateral Common Carotid Arteries
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Accession number;04A0864556
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| Title;Effect of Ibudilast on Learning and Memory in Rats with Ligation of Bilateral Common Carotid Arteries |
| Author;
YAMAZAKI TAKANOBU
(Kyorin Phamaceutical Co., Ltd., Res. Center, JPN)
MASADA KIMIYA
(Kyorin Phamaceutical Co., Ltd., Res. Center, JPN)
YAMANISHI ATSUHIRO
(Kyorin Phamaceutical Co., Ltd., Res. Center, JPN)
MATSUZAWA SHIGEKI
(Kyorin Phamaceutical Co., Ltd., Res. Center, JPN)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.32;NO.10;PAGE.647-653(2004)
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| Figure&Table&Reference;FIG.3, REF.28 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We examined the effect of ibudilast, a phosphodiesterase inhibitor, on impairment of learning and memory in rats with chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was induced by ligation of bilateral common carotid arteries in rats (2VO rats) under anesthesia. The vehicle (0.3% CMC) or ibudilast (10 and 30mg/kg) was orally administered one hour before ligation, and thereafter once daily for 6 days. All evaluation or measurement was performed on the next day of the final administration (i.e., seven days after ligation). Parameters for evaluation were passive avoidance response and long-term potentiation (LTP). At the same time, hippocampal cAMP contents were measured as a biochemical parameter. Passive avoidance response and LTP were significantly impaired in these rats seven days after ligation compared with sham-operated rats. Seven-day treatment with ibudilast (30mg/kg) significantly improved the impairment of passive avoidance response and LTP. Hippocampal cAMP contents tended to increase in the group treated with 30mg/kg of ibudilast, though not statistically significant from the control groups. When hippocampal tissues from rats treated with ibudilast (30mg/kg) for seven days were incubated in the presence of forskolin, cAMP contents significantly increased, as compared with those from control rats. These results indicate that ligation of bilateral common carotid arteries induces behavioral and electropharmacological impairment in rats, and that ibudilast improves this impairment. This suggests that chronic cerebral hypoperfusion could play an important role in development of dementia, and that ibudilast may be effective for dementia of this type. (author abst.) |
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