Partial Preventive Effect of Ibuprofen in a Mouse Model of Vascular Cognitive Impairment Induced by Unilateral Common Carotid Artery Occlusion
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 hr, 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. Conclusions: 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.
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 hr, 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. Conclusions: 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.
참고문헌 (18)
- Geldmacher DS, "Evaluation of dementia", N Engl J Med, 335, pp.330~336 (1996)
- Ikeda M, "Increased prevalence of vascular dementia in Japan: a community-based epidemiological study", Neurology, 57, pp.839~844 (2001)
- Lee AY, "New treatment of vascular cognitive impairment", J Korean Dementia Assoc, 4, pp.63~67 (2005)
- Roma@n GC, "Vascular dementia prevention: a risk factor analysis", Cerebrovasc Dis, 20, pp.91~100 (2005)
- Akiguchi I, "Alterations in glia and axons in the brains of Binswanger’s disease patients", Stroke, 28, pp.1423~1429 (1997)
- Shibata M, "White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion", Stroke, 35, pp.2598~2603 (2004)
- Farkas E, "Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain", Acta Neuropathol, 108, pp.57~64 (2004)
- Yoshizaki K, "Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice", Exp Neurol, 210, pp.585~591 (2008)
- Ennaceur A, "A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data", Behav Brain Res, 31, pp.47~59 (1988)
- Sarti C, "Persistent impairment of gait performances and working memory after bilateral common carotid artery occlusion in the adult Wistar rat", Behav Brain Res, 136, pp.13~20 (2002)
- Roma@n GC, "Brain hypoperfusion: a critical factor in vascular dementia", Neurol Res, 26, pp.454~458 (2004)
- Kato H, "Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using Tc-HMPAO SPECT", Cerebrovasc Dis, 26, pp.556~562 (2008)
- Miki K, "Intensity of chronic cerebral hypoperfusion determines white", gray matter injury and cognitive, J Neurosci Res, pp.2009, 87[DOI]
- Tamaki M, "Carotid artery occlusion and collateral circulation in C57Black", 6J mice detected by synchrotron radiation microangiography, 2006, pp.52, 111~118
- Dirnagl U, "Pathobiology of ischaemic stroke: an integrated view", Trends Neurosci, 22, pp.391~397 (1999)
- Farkas E, "Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases", Brain Res Rev, 54, pp.162~180 (2007)
- Liu HX, "Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment", Mol Brain Res, 139, pp.169~177 (2005)
- Thiel G, "Synapsin I, synapsin II, and synaptophysin: marker proteins of synaptic vesicles", Brain Pathol, 3, pp.87~95 (1993)