Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9416199 | Brain Research | 2005 | 10 Pages |
Abstract
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 2α (p-eIF2α), 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-eIF2α, 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.
Keywords
CBFdouble-stranded RNA-activated protein kinase (PKR)-like ER kinaseATF-4eIF2αUPRRyRMCAOTTCGFAPPVDFPBSMCASDS2,3,5-triphenyltetrazolium chlorideC/EBP-homologous proteinCa2+DMSODisorders of the nervous systemmiddle cerebral artery occlusionIschemiaANOVATerminal deoxynucleotidyl transferase-mediated dUTP nick end labelingTUNELCHOPcerebral blood flowApoptosisDantroleneDimethyl sulfoxidesodium dodecyl sulfateendoplasmic reticulummiddle cerebral arteryeukaryotic initiation factor 2αactivating transcription factor-4Phosphate-buffered salineRatUnfolded protein responseGlial fibrillary acidic proteinPERKsham controlRyanodine receptorCalcium ions
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Authors
Feng Li, Takeshi Hayashi, Guang Jin, Kentaro Deguchi, Shoko Nagotani, Isao Nagano, Mikio Shoji, Pak H. Chan, Koji Abe,