机构:[1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China神经外科首都医科大学宣武医院[2]Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China[3]Department of Neurology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China[4]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China中美神经科学研究所首都医科大学宣武医院
Background: We showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia. Methods: Rats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO). Neurological deficit score, infarct size, apoptosis level, brain water content and Evans Blue extravasation were assessed at 24 h after stroke. Expressions of occludin and zonula occludens 1 (ZO-1), collagen IV, aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9) and MMP-2 were assessed by Western blotting. Results: 2-BFI treatment was associated with significant improvement of neurological performance and decreased infarct volume at 24 h after stroke. Apoptosis level reduced significantly by 2-BFI compared to the vehicle group (34.3 +/- 5.4% vs 56.1 +/- 7.9%, p < 0.05). Significant decreased of brain water content (79.5 +/- 2.6% vs 84.62 +/- 2%, p < 0.05) and Evans Blue extravasation (1.2 +/- 0.5 vs 2.5 +/- 0.41 mu g/g, p < 0.05) of ipsilateral hemisphere was observed in 2-BFI group compared to vehicle group. Expressions of occludin, ZO-1 and collagen IV were significantly higher while MMP-9 level significantly lower in 2-BFI group. AQP-4 and MMP-2 showed no difference between 2-BFI and the vehicle groups. Conclusions: These results suggest that the neuroprotective effects of 2-BFI in acute ischemic brain damage are at least partly due to the drug's ability to improve the functions of NVU.
基金:
the China National Funds for Distinguished Young Scientists (81325007),
the Distinguished Professor of Cheung Kong Scholars Program (T2014251),
the National Natural Science Foundation of China (81571114),
the Wenzhou Municipal Sci-Tech Bureau Program (Y20120154 and Y20140686),
the National Natural Science Foundation of China Projects for International Cooperation and Exchange (81620108011).
第一作者机构:[1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China[2]Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
通讯作者:
通讯机构:[*1]Department of Neurology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xue Yuan Xi Lu #109, 325027, Wenzhou, China[*2]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Chang Chun Street #2, 100000, Beijing, China.
推荐引用方式(GB/T 7714):
Zheng Zhang ,Linlei Zhang ,Jiaou Chen ,et al.2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia[J].JOURNAL OF STROKE & CEREBROVASCULAR DISEASES.2018,27(6):1481-1489.doi:10.1016/j.jstrokecerebrovasdis.2017.12.041.
APA:
Zheng Zhang,,Linlei Zhang,,Jiaou Chen,,Yungang Cao,,Man Qu,...&Xunming Ji.(2018).2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia.JOURNAL OF STROKE & CEREBROVASCULAR DISEASES,27,(6)
MLA:
Zheng Zhang,,et al."2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia".JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 27..6(2018):1481-1489