PMID- 28069373
OWN - NLM
STAT- MEDLINE
DCOM- 20170518
LR  - 20200319
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 351
IP  - 2
DP  - 2017 Feb 15
TI  - Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway 
      in an experimental model of ischemic stroke.
PG  - 163-172
LID - S0014-4827(16)30450-5 [pii]
LID - 10.1016/j.yexcr.2016.12.028 [doi]
AB  - Ischemic stroke, the second leading cause of death worldwide, leads to excessive 
      glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and 
      massive influx of calcium (Ca(2+)), which may activate calpain and caspase-3, 
      resulting in cellular damage and death. Memantine is an uncompetitive NMDAR 
      antagonist with low-affinity/fast off-rate. We investigated the potential 
      mechanisms through which memantine protects against ischemic stroke in vitro and 
      in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to 
      establish an experimental model of ischemic stroke. The neuroprotective effects 
      of memantine on ischemic rats were evaluated by neurological deficit scores and 
      infarct volumes. The activities of calpain and caspase-3, and expression levels 
      of microtubule-associated protein-2 (MAP2) and postsynaptic density-95 (PSD95) 
      were determined by Western blotting. Additionally, Nissl staining and 
      immunostaining were performed to examine brain damage, cell apoptosis, and 
      neuronal loss induced by ischemia. Our results show that memantine could 
      significantly prevent ischemic stroke-induced neurological deficits and brain 
      infarct, and reduce ATP depletion-induced neuronal death. Moreover, memantine 
      markedly suppressed the activation of the calpain-caspase-3 pathway and cell 
      apoptosis, and consequently, attenuated brain damage and neuronal loss in MCAO 
      rats. These results provide a molecular basis for the role of memantine in 
      reducing neuronal apoptosis and preventing neuronal damage, suggesting that 
      memantine may be a promising therapy for stroke patients.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Chen, Bin
AU  - Chen B
AD  - Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian 
      Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function 
      Rehabilitation, Academy of Integrative Medicine Biomedical Research Center, 
      Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; 
      Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, 
      Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 
      200032, China.
FAU - Wang, Guoxiang
AU  - Wang G
AD  - Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, 
      Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 
      200032, China.
FAU - Li, Weiwei
AU  - Li W
AD  - Department of Anesthesiology, Shanghai Changzheng Hospital, Shanghai 200003, 
      China.
FAU - Liu, Weilin
AU  - Liu W
AD  - Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian 
      Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function 
      Rehabilitation, Academy of Integrative Medicine Biomedical Research Center, 
      Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
FAU - Lin, Ruhui
AU  - Lin R
AD  - Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian 
      Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function 
      Rehabilitation, Academy of Integrative Medicine Biomedical Research Center, 
      Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
FAU - Tao, Jing
AU  - Tao J
AD  - Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian 
      Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function 
      Rehabilitation, Academy of Integrative Medicine Biomedical Research Center, 
      Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
FAU - Jiang, Min
AU  - Jiang M
AD  - Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, 
      Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 
      200032, China.
FAU - Chen, Lidian
AU  - Chen L
AD  - Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian 
      Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function 
      Rehabilitation, Academy of Integrative Medicine Biomedical Research Center, 
      Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. 
      Electronic address: fjtcm1958@sina.com.
FAU - Wang, Yun
AU  - Wang Y
AD  - Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, 
      Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 
      200032, China. Electronic address: yunwang@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170106
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Culture Media)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (MAP2 protein, rat)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.22.- (Calpain)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - Adenosine Triphosphate/deficiency
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain Ischemia/*drug therapy/genetics/metabolism/pathology
MH  - Calpain/antagonists & inhibitors/*genetics/metabolism
MH  - Caspase 3/*genetics/metabolism
MH  - Cerebral Arteries/surgery
MH  - Cerebrovascular Disorders/surgery
MH  - Culture Media/pharmacology
MH  - Disks Large Homolog 4 Protein
MH  - Gene Expression Regulation
MH  - Glucose/deficiency
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Memantine/*pharmacology
MH  - Membrane Proteins/genetics/metabolism
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Primary Cell Culture
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Stroke/*drug therapy/genetics/metabolism/pathology
OTO - NOTNLM
OT  - Apoptosis
OT  - Calpain
OT  - Caspase-3
OT  - Ischemic stroke
OT  - Memantine
EDAT- 2017/01/11 06:00
MHDA- 2017/05/19 06:00
CRDT- 2017/01/11 06:00
PHST- 2016/11/16 00:00 [received]
PHST- 2016/12/29 00:00 [revised]
PHST- 2016/12/31 00:00 [accepted]
PHST- 2017/01/11 06:00 [pubmed]
PHST- 2017/05/19 06:00 [medline]
PHST- 2017/01/11 06:00 [entrez]
AID - S0014-4827(16)30450-5 [pii]
AID - 10.1016/j.yexcr.2016.12.028 [doi]
PST - ppublish
SO  - Exp Cell Res. 2017 Feb 15;351(2):163-172. doi: 10.1016/j.yexcr.2016.12.028. Epub 
      2017 Jan 6.