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2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia

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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 [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
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关键词: Focal ischemia 2-(2-benzofuranyl)-2-imidazoline neurovascular unit blood-brain barrier neuroprotection

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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.

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出版当年[2017]版:
大类 | 4 区 医学
小类 | 4 区 神经科学 4 区 外周血管病
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 神经科学 4 区 外周血管病
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出版当年[2016]版:
Q4 PERIPHERAL VASCULAR DISEASE Q4 NEUROSCIENCES
最新[2023]版:
Q3 NEUROSCIENCES Q3 PERIPHERAL VASCULAR DISEASE

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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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.
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