PMID- 15921666
OWN - NLM
STAT- MEDLINE
DCOM- 20050914
LR  - 20131121
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1048
IP  - 1-2
DP  - 2005 Jun 28
TI  - The protective effect of dantrolene on ischemic neuronal cell death is associated 
      with reduced expression of endoplasmic reticulum stress markers.
PG  - 59-68
AB  - The endoplasmic reticulum (ER) plays an important role in ischemic neuronal cell 
      death. In order to determine the effect of dantrolene, a ryanodine receptor 
      antagonist, on ER stress response and ischemic brain injury, we investigated 
      changes in ER stress-related molecules, that is phosphorylated form of 
      double-stranded RNA-activated protein kinase (PKR)-like ER kinase (p-PERK), 
      phosphorylated form of eukaryotic initiation factor 2alpha (p-eIF2alpha), 
      activating transcription factor-4 (ATF-4), and C/EBP-homologous protein (CHOP), 
      as well as terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL) in the peri-ischemic area and ischemic core region of rat brain after 
      transient middle cerebral artery occlusion (MCAO). In contrast to the cases 
      treated with vehicle, the infarct volume and TUNEL-positive cells were 
      significantly reduced at 24 h of reperfusion by treatment with dantrolene. The 
      immunoreactivities for p-PERK, p-eIF2alpha, ATF-4, and CHOP were increased at the 
      ischemic peripheral region after MCAO, which were partially inhibited by 
      dantrolene treatment. The present results suggest that dantrolene significantly 
      decreased infarct volume and provided neuroprotective effect on rats after 
      transient MCAO by reducing ER stress-mediated apoptotic signal pathway activation 
      in the ischemic area.
FAU - Li, Feng
AU  - Li F
AD  - Department of Neurology, Okayama University Graduate School of Medicine and 
      Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
FAU - Hayashi, Takeshi
AU  - Hayashi T
FAU - Jin, Guang
AU  - Jin G
FAU - Deguchi, Kentaro
AU  - Deguchi K
FAU - Nagotani, Shoko
AU  - Nagotani S
FAU - Nagano, Isao
AU  - Nagano I
FAU - Shoji, Mikio
AU  - Shoji M
FAU - Chan, Pak H
AU  - Chan PH
FAU - Abe, Koji
AU  - Abe K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Atf4 protein, rat)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Muscle Relaxants, Central)
RN  - 0 (Transcription Factors)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
RN  - F64QU97QCR (Dantrolene)
SB  - IM
MH  - Activating Transcription Factor 4
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western/methods
MH  - CCAAT-Enhancer-Binding Proteins/metabolism
MH  - Cell Count/methods
MH  - Cell Death/drug effects
MH  - Dantrolene/*therapeutic use
MH  - Disease Models, Animal
MH  - Endoplasmic Reticulum/drug effects/*metabolism
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Immunohistochemistry/methods
MH  - In Situ Nick-End Labeling/methods
MH  - Infarction, Middle Cerebral Artery/complications
MH  - Ischemia/etiology/pathology/*prevention & control
MH  - Male
MH  - Muscle Relaxants, Central/*therapeutic use
MH  - Neurons/*drug effects
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion/methods
MH  - Time Factors
MH  - Transcription Factor CHOP
MH  - Transcription Factors/metabolism
MH  - eIF-2 Kinase/metabolism
EDAT- 2005/06/01 09:00
MHDA- 2005/09/15 09:00
CRDT- 2005/06/01 09:00
PHST- 2005/02/09 00:00 [received]
PHST- 2005/04/11 00:00 [revised]
PHST- 2005/04/15 00:00 [accepted]
PHST- 2005/06/01 09:00 [pubmed]
PHST- 2005/09/15 09:00 [medline]
PHST- 2005/06/01 09:00 [entrez]
AID - S0006-8993(05)00607-4 [pii]
AID - 10.1016/j.brainres.2005.04.058 [doi]
PST - ppublish
SO  - Brain Res. 2005 Jun 28;1048(1-2):59-68. doi: 10.1016/j.brainres.2005.04.058.