PMID- 23562504
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20181202
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 543
DP  - 2013 May 24
TI  - Edaravone alleviates hypoxia-acidosis/reoxygenation-induced neuronal injury by 
      activating ERK1/2.
PG  - 72-7
LID - S0304-3940(13)00261-9 [pii]
LID - 10.1016/j.neulet.2013.02.067 [doi]
AB  - Edaravone, a free radical scavenger, is the first clinical drug of 
      neuroprotection for ischemic stroke patients in the world, and has been shown to 
      be an effective agent to alleviate cerebral ischemic injury. It has been 
      established that acidosis is a common feature of cerebral ischemia and underlies 
      the pathogenesis of ischemic stroke. In the present study, we investigated the 
      role of edaravone in hypoxia-acidosis/reoxygenation (H-A/R)-induced neuronal 
      injury that is partially mediated by the activation of acid-sensing ion channels 
      (ASICs). Here, we observed that pretreatment of cultured neurons with edaravone 
      largely reduced LDH release induced by acidosis or H-A/R. We also found that 
      edaravone exhibited its neuroprotective roles by enhancing brain-derived 
      neurotrophic factor (BDNF) and Bcl-2 expression, suppressing caspase-3 activity 
      and promoting extracellular signal-regulated kinase1/2 (ERK1/2) activation. 
      Furthermore, the addition of MEK (mitogen-activated protein kinase/ERK kinase) 
      antagonists PD98059 and U0126 nearly abolished the beneficial effects of 
      edaravone. Similarly, ASICs blockade produced the protective effects comparable 
      to edaravone administration. These results indicate that edaravone is capable of 
      attenuating H-A/R-mediated neurotoxicity at least partially through activating 
      ERK1/2.
CI  - Crown Copyright (c) 2013. Published by Elsevier Ireland Ltd. All rights reserved.
FAU - Wang, Guibin
AU  - Wang G
AD  - Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya 
      Road, Changsha, Hunan 410008, China.
FAU - Su, Jingjing
AU  - Su J
FAU - Li, Lingjuan
AU  - Li L
FAU - Feng, Jie
AU  - Feng J
FAU - Shi, Lei
AU  - Shi L
FAU - He, Wei
AU  - He W
FAU - Liu, Yunhai
AU  - Liu Y
LA  - eng
PT  - Journal Article
DEP - 20130402
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - S798V6YJRP (Edaravone)
RN  - S88TT14065 (Oxygen)
RN  - T3CHA1B51H (Antipyrine)
SB  - IM
MH  - Acidosis/*metabolism
MH  - Animals
MH  - Antipyrine/*analogs & derivatives/pharmacology
MH  - Brain Ischemia/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Edaravone
MH  - Enzyme Activation
MH  - Glucose/metabolism
MH  - Hydrogen-Ion Concentration
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Oxygen/metabolism
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
EDAT- 2013/04/09 06:00
MHDA- 2013/09/07 06:00
CRDT- 2013/04/09 06:00
PHST- 2012/12/06 00:00 [received]
PHST- 2013/02/20 00:00 [revised]
PHST- 2013/02/23 00:00 [accepted]
PHST- 2013/04/09 06:00 [entrez]
PHST- 2013/04/09 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
AID - S0304-3940(13)00261-9 [pii]
AID - 10.1016/j.neulet.2013.02.067 [doi]
PST - ppublish
SO  - Neurosci Lett. 2013 May 24;543:72-7. doi: 10.1016/j.neulet.2013.02.067. Epub 2013 
      Apr 2.