PMID- 29398538
OWN - NLM
STAT- MEDLINE
DCOM- 20180911
LR  - 20180911
IS  - 1532-8511 (Electronic)
IS  - 1052-3057 (Linking)
VI  - 27
IP  - 6
DP  - 2018 Jun
TI  - 2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the 
      Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia.
PG  - 1481-1489
LID - S1052-3057(17)30715-2 [pii]
LID - 10.1016/j.jstrokecerebrovasdis.2017.12.041 [doi]
AB  - 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 microg/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.
CI  - Copyright (c) 2018 National Stroke Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Zhang, Zheng
AU  - Zhang Z
AD  - Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 
      China; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Zhang, Linlei
AU  - Zhang L
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Chen, Jiaou
AU  - Chen J
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Cao, Yungang
AU  - Cao Y
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Qu, Man
AU  - Qu M
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Lin, Xinda
AU  - Lin X
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Han, Zhao
AU  - Han Z
AD  - Department of Neurology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address: 
      wzhanzhao@aliyun.com.
FAU - Ji, Xunming
AU  - Ji X
AD  - Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 
      China; China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical 
      University, Beijing, China. Electronic address: jixm@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180203
PL  - United States
TA  - J Stroke Cerebrovasc Dis
JT  - Journal of stroke and cerebrovascular diseases : the official journal of National 
      Stroke Association
JID - 9111633
RN  - 0 (Benzofurans)
RN  - 0 (Imidazoles)
RN  - 0 (Neuroprotective Agents)
RN  - 72583-92-7 (2-(2-benzofuranyl)-2-imidazoline)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Benzofurans/*pharmacology
MH  - Brain/blood supply/*drug effects/metabolism/pathology
MH  - Brain Edema/drug therapy/etiology/metabolism/pathology
MH  - Brain Ischemia/complications/*drug therapy/metabolism/pathology
MH  - Capillary Permeability/drug effects/physiology
MH  - Disease Models, Animal
MH  - Imidazoles/*pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotection/drug effects/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - 2-(2-benzofuranyl)-2-imidazoline
OT  - Focal ischemia
OT  - blood-brain barrier
OT  - neuroprotection
OT  - neurovascular unit
EDAT- 2018/02/06 06:00
MHDA- 2018/09/12 06:00
CRDT- 2018/02/06 06:00
PHST- 2017/10/18 00:00 [received]
PHST- 2017/12/14 00:00 [revised]
PHST- 2017/12/23 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2018/09/12 06:00 [medline]
PHST- 2018/02/06 06:00 [entrez]
AID - S1052-3057(17)30715-2 [pii]
AID - 10.1016/j.jstrokecerebrovasdis.2017.12.041 [doi]
PST - ppublish
SO  - J Stroke Cerebrovasc Dis. 2018 Jun;27(6):1481-1489. doi: 
      10.1016/j.jstrokecerebrovasdis.2017.12.041. Epub 2018 Feb 3.