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Partial Preventive Effect of Ibuprofen in a Mouse Model of Vascular Cognitive Impairment Induced by Unilateral Common Carotid Artery Occlusion

Authors
Lee, JS; Im, DS; Moon, GJ; Gwag, BJ; Moon, SY; Hong, JM; Joo, IS
Citation
Dementia and neurocognitive disorders, 8(2):104-111, 2009
Journal Title
Dementia and neurocognitive disorders
ISSN
1738-14952384-0757
Abstract
Background: Vascular cognitive impairment (VCI) has been shown to be related to inflammation in previous clinical and animal studies. A recent study showed VCI and increase in inflammatory cytokines in a mouse model of right common carotid artery occlusion (rCCAO). We aimed to determine the preventive effect of an anti-inflammatory drug, ibuprofen, on VCI in an rCCAO mouse model.



Methods: C57BL/6 mice were rCCAO- or sham-operated. First, serial object recognition tests with respective vehicle and sham groups of mice were performed weekly to evaluate VCI until 4 weeks after surgery, and the discrimination index was compared. Histological observations were made 3 hours, 1 day, 1 week, and 4 weeks after surgery. Second, object recognition tests and histological studies with three groups of mice were performed 4 months after surgery to evaluate the preventive effect of ibuprofen on VCI. The experimental groups were sham (n = 15), vehicle (rCCAO-operated; n = 15), and ibuprofen (rCCAO-operated, ibuprofen-supplemented chow; n = 15).



Results: Until 4 weeks after rCCAO surgery, the discrimination index was lower in rCCAO-operated mice than in sham-operated mice, and the difference was marginally significant in week 1 (mean ± standard error: 0.35 ± 0.08 for rCCAO vs. 0.68 ± 0.12 for sham; t-test, p = 0.050). The index from week 2 to week 4 tended to be low in rCCAO-operated mice as compared to sham-operated mice, but the difference was not statistically significant. Eosin-positive neurons were not observed at all stages, but activated microglia, which was stained by using antibodies against Iba-1, was observed in some rCCAO-operated mice on day 1 and week 1. The preventive effect of ibuprofen was not sufficient on objective recognition tests (discrimination index, mean ± standard error: sham 0.36 ± 0.10, vehicle 0.01 ± 0.15 and ibuprofen 0.14 ± 0.13; analysis of variance, F = 1.987, p = 0.151), and no specific histological finding was observed 4 months after surgery.



Conslusion: The anti-inflammatory drug ibuprofen was not effective enough to prevent VCI induced by rCCAO. The effects of inflammation seemed to be evident only in the early phase in this model.
Keywords
vascular cognitive impairmentdementiacommon carotid artery occlusionobject recognition testibuprofen
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
이, 진수곽, 병주문, 소영홍, 지만주, 인수
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