지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 284 - 292 (9page)
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초록· 키워드
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Background and Purpose White-matter (WM) lesions are known to potentiate cognitive impairment in poststroke patients. The present study was designed to assess whether Ginkgo biloba extract (GB) and cilostazol, which were evaluated alone and in a combination formula (Renexin), can attenuate the WM lesions and cognitive decline caused by chronic hypoperfusion in the rat.
Methods Animals were divided into five treatment groups: cilostazol (25 mg/kg/day), GB (20mg/kg/day), Renexin (25 mg/kg/day cilostazol + 20 mg/kg/day GB), vehicle, and sham. The animals received the treatments orally 1 day after bilateral common carotid artery occlusion [twovessel occlusion (2VO); except for the sham group, which underwent the surgery but the arteries were not occluded], and then the same dose every day for 21 days thereafter. Prior to sacrificing the rats, repetitive eight-arm radial maze testing was performed to examine their cognitive abilities. After drug administration and cognitive testing, brain tissues were isolated for Klüver-Barrera and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL)staining, immunohistochemical assessment of glial fibrillary acidic protein (GFAP) and CD11b (OX-42), and to assay free-radical scavenging activity.
Results We found that the significant WM lesions induced by 2VO was ameliorated significantly by treatment with cilostazol, GB, and Renexin, in association with increased TUNEL-positive cells. In addition, chronic cerebral hypoperfusion caused a large increase in the degree of GFAP and OX-42 immunoreactivity and free-radical activity in the optic tract. These abnormalities were significantly reversed by the three drugs, but most prominently by Renexin, suggesting a markedly enhanced or supra-additive effect of cilostazol and GB when administered together.
Conclusions Significant attenuation of cytoarchitectural damage and apoptotic cell death was found with GB and cilostazol, but a markedly enhanced effect was seen for treatment with their combination in the WM of rat brains after bilateral occlusion of the common carotid arteries.
We suggest that combination therapy with GB and cilostazol provides enhanced neuroprotective effects and induces subsequent cognitive improvement in patients with chronic ischemic conditions.
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참고문헌 (22)
참고문헌 신청
Beal MF / 1993 / Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? / Trends Neurosci 16 : 125 ~ 131
Bennett SA / 1998 / Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment / Neuroreport 9 : 161 ~ 166
Davidson CM / 2000 / Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration / Brain Res 859 : 96 ~ 103
Esterbauer H / 1991 / Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes / Free Radic Biol Med 11 : 81 ~ 128
Ihara M / 2001 / Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter / J Cereb Blood Flow Metab 2
Bennett SA / 1998 / Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment / Neuroreport 9 : 161 ~ 166
Davidson CM / 2000 / Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration / Brain Res 859 : 96 ~ 103
Esterbauer H / 1991 / Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes / Free Radic Biol Med 11 : 81 ~ 128
Ihara M / 2001 / Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter / J Cereb Blood Flow Metab 2
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