|
|
|
|
Sac-1004,a vascular leakage blocker,reduces cerebral ischemia-reperfusion injury by suppressing blood-brain barrier disruption and inflammation
|
|
|
|
|
|
|
|
نویسنده
|
zhang h. ,park j.h. ,maharjan s. ,park j.a. ,choi k.-s. ,park h. ,jeong y. ,ahn j.h. ,kim i.h. ,lee j.-c. ,cho j.h. ,lee i.-k. ,lee c.h. ,hwang i.k. ,kim y.-m. ,suh y.-g. ,won m.-h. ,kwon y.-g.
|
|
منبع
|
journal of neuroinflammation - 2017 - دوره : 14 - شماره : 1
|
|
چکیده
|
Background: blood-brain barrier (bbb) breakdown and inflammation are critical events in ischemic stroke,contributing to aggravated brain damage. the bbb mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. thus,the maintenance of bbb integrity may be a potential target for neuroprotection. sac-1004,a pseudo-sugar derivative of cholesterol,enhances the endothelial barrier by the stabilization of the cortical actin ring. results: here,we report on the protective effects of sac-1004 on cerebral ischemia-reperfusion (i/r) injury. treatment with sac-1004 significantly blocked the interleukin-1β-induced monolayer hyperpermeability of human brain microvascular endothelial cells (hbmecs),loss of tight junctions,and formation of actin stress fiber. sac-1004 suppressed the expression of adhesion molecules,adhesion of u937 cells,and activation of nuclear factor-κb in hbmecs. using a rat model of transient focal cerebral ischemia,it was shown that sac-1004 effectively ameliorated neurological deficits and ischemic damage. in addition,sac-1004 decreased bbb leakage and rescued tight junction-related proteins. moreover,the staining of cd11b and glial fibrillary acidic protein showed that sac-1004 inhibited glial activation. conclusions: taken together,these results demonstrate that sac-1004 has neuroprotective activities through maintaining bbb integrity,suggesting that it is a great therapeutic candidate for stroke. © 2017 the author(s).
|
|
کلیدواژه
|
Blood-brain barrier; Cerebral ischemia; Inflammation; Neuroprotection; Sac-1004; Tight junction
|
|
آدرس
|
yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, hallym university,department of biomedical science and research institute for bioscience and biotechnology,chuncheon,24252, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea, hallym university,department of biomedical science and research institute for bioscience and biotechnology,chuncheon,24252, South Korea, kangwon national university,department of neurobiology,school of medicine,chuncheon,24341, South Korea, kangwon national university,department of neurobiology,school of medicine,chuncheon,24341, South Korea, kangwon national university,department of neurobiology,school of medicine,chuncheon,24341, South Korea, kyungpook national university,department of internal medicine,school of medicine,daegu,700-721, South Korea, dankook university,department of pharmacy,college of pharmacy,cheonan,31116, South Korea, seoul national university,department of anatomy and cell biology,college of veterinary medicine,and research institute for veterinary science,seoul,08826, South Korea, kangwon national university,vascular system research center,chuncheon,kangwon,24341, South Korea, seoul national university,colleges of pharmacy,seoul,151-742, South Korea, kangwon national university,department of neurobiology,school of medicine,chuncheon,24341, South Korea, yonsei university,department of biochemistry,college of life science and biotechnology,seoul,120-749, South Korea
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|