PMID- 24752488
OWN - NLM
STAT- MEDLINE
DCOM- 20150814
LR  - 20211021
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 54
IP  - 4
DP  - 2014 Dec
TI  - Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the 
      expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats.
PG  - 591-601
LID - 10.1007/s12031-014-0307-6 [doi]
AB  - Excitotoxicity and cytotoxic edema are the two major factors resulting in 
      neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent 
      protein kinase II (CaMK II), the downstream signal molecular of 
      N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. 
      Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to 
      control the flux of water. In a previous study, we had reported that pretreatment 
      of simvastatin protected the cerebrum from ischemia and reperfusion injury by 
      decreasing neurological deficit score and infarct area (Zhu et al. PLoS One 
      7:e51552, 2012). The present study used a middle cerebral artery occlusion (MCAO) 
      model to further explore the pleiotropic effect of simvastatin via CaMK II and 
      AQP4. The results showed that simvastatin reduced degenerated cells and brain 
      edema while decreasing the protein expressions of phosphor-CaMK II and AQP4, and 
      increasing the ratios of Bcl-2/Bax, which was independent of cholesterol-lowering 
      effect. Immunocomplexes formed between the subunit of NMDARs-NR3A and AQP4 were 
      detected for the first time. It was concluded that simvastatin could protect the 
      cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the 
      expressions of phosphor-CaMK II and AQP4, and that the interaction between NR3A 
      and AQP4 might provide the base for AQP4 involving in the signaling pathways 
      mediated by NMDARs.
FAU - Zhu, Min-xia
AU  - Zhu MX
AD  - Medical College of Tibet University for Nationalities, Xianyang, Shaanxi, China, 
      zhuminxia2001@163.com.
FAU - Lu, Chao
AU  - Lu C
FAU - Xia, Chun-mei
AU  - Xia CM
FAU - Qiao, Zhong-wei
AU  - Qiao ZW
FAU - Zhu, Da-nian
AU  - Zhu DN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140423
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Aqp4 protein, rat)
RN  - 0 (Aquaporin 4)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (NR3A NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Animals
MH  - Aquaporin 4/genetics/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism
MH  - Cerebrum/cytology/drug effects/*metabolism
MH  - Cholesterol/metabolism
MH  - Down-Regulation
MH  - Hypolipidemic Agents/*pharmacology/therapeutic use
MH  - Infarction, Middle Cerebral Artery/*metabolism/prevention & control
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Simvastatin/*pharmacology/therapeutic use
EDAT- 2014/04/23 06:00
MHDA- 2015/08/15 06:00
CRDT- 2014/04/23 06:00
PHST- 2014/02/09 00:00 [received]
PHST- 2014/04/08 00:00 [accepted]
PHST- 2014/04/23 06:00 [entrez]
PHST- 2014/04/23 06:00 [pubmed]
PHST- 2015/08/15 06:00 [medline]
AID - 10.1007/s12031-014-0307-6 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2014 Dec;54(4):591-601. doi: 10.1007/s12031-014-0307-6. Epub 2014 
      Apr 23.