PMID- 28132912
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20220317
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 798
DP  - 2017 Mar 5
TI  - Involvement of arterial baroreflex and nicotinic acetylcholine receptor alpha7 
      subunit pathway in the protection of metformin against stroke in stroke-prone 
      spontaneously hypertensive rats.
PG  - 1-8
LID - S0014-2999(17)30043-2 [pii]
LID - 10.1016/j.ejphar.2017.01.035 [doi]
AB  - Stroke is a leading cause of mortality and disability worldwide. There is growing 
      evidence that metformin (Met) has potent neuroprotective effects; however, its 
      mechanisms remain unclear. We examined the role of the arterial baroreflex and 
      cholinergic-alpha7 nicotinic acetylcholine receptor (alpha7nAChR) anti-inflammory pathway 
      in the beneficial effects of Met against stroke. Stroke-prone spontaneously 
      hypertensive rats (SHRSP) were used to observe stroke development indicated by 
      lifespan of SHRSP and the ischemic injury induced by permanent middle cerebral 
      artery occlusion (MCAO). Sinoaortic denervation was used to inactivate the 
      arterial baroreflex. MCAO were also performed in alpha7nAChR knockout (KO) mice. 
      Briefly, Met increased the life span of SHRSP and reduced the infarct area 
      induced by MCAO. Met also improved the function of arterial baroreflex. The 
      beneficial effects of Met on stroke were markedly attenuated by blunting the 
      arterial baroreflex. Met up-regulated the expression of vesicular acetylcholine 
      transporter (VAChT) and alpha7nAChR, down-regulated the level of pro-inflammtory 
      cytokines in serum and peri-infarct of ischemic brain. Arterial baroreflex 
      dysfunction decreased the expression of VAchT and alpha7nAChR, showed upward tendency 
      in the level of pro-inflammtory cytokines. Most importantly, arterial baroreflex 
      dysfunction nearly abolished such effect of Met on cholinergic signaling. In 
      addition, the alpha7nAChR KO mice also had significantly worse ischemic damage 
      induced by MCAO, and neuroprotection of Met disappeared in alpha7nAChR KO mice. In 
      conclusion, Met improved the arterial baroreflex function, and then enhancing 
      cholinergic anti-inflammatory pathway in an alpha7nAChR-dependent manner, thereby 
      effectively prevent ischemic induced brain injury and delayed stroke onset in 
      SHRSP.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Guo, Jin-Min
AU  - Guo JM
AD  - Department of Pharmacology, Jinan Military General Hospital, Jinan, Shandong, 
      China.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Pharmacology, Jinan Military General Hospital, Jinan, Shandong, 
      China.
FAU - Niu, Xue-Cai
AU  - Niu XC
AD  - Department of Radiotheropy, The Forth Hospital of Jinan City, Jinan, Shandong, 
      China.
FAU - Shu, He
AU  - Shu H
AD  - Department of Pharmacology, Jinan Military General Hospital, Jinan, Shandong, 
      China.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Orthopaedics, Jinan Military General Hospital, Jinan, Shandong, 
      China.
FAU - Su, Ding-Feng
AU  - Su DF
AD  - Department of Pharmacology, School of Pharmacy, Second Military Medical 
      University, Shanghai, China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Pharmacology, School of Pharmacy, Second Military Medical 
      University, Shanghai, China.
FAU - Liu, Ai-Jun
AU  - Liu AJ
AD  - Department of Pharmacology, School of Pharmacy, Second Military Medical 
      University, Shanghai, China.
FAU - Zhu, De-Qiu
AU  - Zhu DQ
AD  - Division of Pharmacy, Tongji Hospital, Tongji University School of Medicine, 389 
      Xin Cun Road, Shanghai 200065, China. Electronic address: zdq_0726@163.com.
FAU - Xu, Jian-Jiang
AU  - Xu JJ
AD  - Department of Pharmacology, Jinan Military General Hospital, Jinan, Shandong, 
      China. Electronic address: xjj8605@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170126
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cytokines)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Slc18a3 protein, rat)
RN  - 0 (Vesicular Acetylcholine Transport Proteins)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Arteries/*drug effects/physiopathology
MH  - Baroreflex/*drug effects
MH  - Brain Ischemia/complications
MH  - Cytokines/blood
MH  - Disease Susceptibility
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knockout Techniques
MH  - Male
MH  - Metformin/*pharmacology
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Stroke/complications/metabolism/*physiopathology/*prevention & control
MH  - Vesicular Acetylcholine Transport Proteins/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/deficiency/genetics/*metabolism
OTO - NOTNLM
OT  - Arterial baroreflex
OT  - Metformin
OT  - Nicotinic acetylcholine receptor alpha7 subunit
OT  - Stoke
OT  - Stroke-prone spontaneously hypertensive rats
EDAT- 2017/01/31 06:00
MHDA- 2017/05/16 06:00
CRDT- 2017/01/31 06:00
PHST- 2016/11/03 00:00 [received]
PHST- 2017/01/20 00:00 [revised]
PHST- 2017/01/25 00:00 [accepted]
PHST- 2017/01/31 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2017/01/31 06:00 [entrez]
AID - S0014-2999(17)30043-2 [pii]
AID - 10.1016/j.ejphar.2017.01.035 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 Mar 5;798:1-8. doi: 10.1016/j.ejphar.2017.01.035. Epub 2017 
      Jan 26.