[Effects of edaravone on IRE1 mRNA expression and neuronal apoptosis in the hippocampus of rats with status convulsivus].
OBJECTIVE
To investigate the expression of the key marker of endoplasmic reticulum stress (ERS) IRE1 mRNA and neuronal apoptosis in the rat hippocampus after status convulsivus (SC), and the intervention effects of edaravone, a novel free radical scavenger.


METHODS
Sprague-Dawley (SD) rats aged 19-21 days were randomly assigned to three groups: normal control, SC and edaravone-treated SC. SC was induced in the later two groups. The two groups were subdivided into 5 groups sacrificed at 4, 12, 24, 48, and 72 hrs after SC induction. IRE1 mRNA expression in the hippocampus was detected by RT-PCR. Neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The ultramicrostructural changes of neuron were observed by electron microscopy.


RESULTS
IRE1 mRNA expression was obviously up-regulated 4 and 12 hrs after SC compared with the normal control group (P<0.01). IRE1 mRNA expression in the edaravone-treated SC group was notably higher than the untreated SC group 4, 12 and 24 hrs after SC and the normal control group (P<0.01). TUNEL positive cells in the hippocampus in the untreated SC group were significantly more than those in the normal control group (P<0.01). The number of TUNEL positive cells increased with the prolonged convulsion time. TUNEL positive cells in the edaravone-treated SC group were significantly reduced compared with those in the untreated SC group 12, 24, 48 and 72 hrs after SC (P<0.05 or P<0.01), but remained higher than the normal control group (P<0.05 or P<0.01). The peri-nucleus cell organ injuries were observed 4 hrs after SC and karyopycnosis and cytoplasm condensation were observed 12 hrs after SC in the SC and the edaravone-treated SC groups. The edaravone-treated SC group demonstrated less severe apoptosis than the untreated SC group.


CONCLUSIONS
Edaravone may have neuroprotections against SC by an up-regulation of IRE1 expression. It might serve as an effective agent for reducing ERS in vivo.
Jiao
Ying
Y
Department of Pediatric Neurology, Yuying Children's Hospital Affiliated to Wenzhou Medical College, Wenzhou, Zhejiang 325027, China.
Deng
Xiao-Long
XL
Li
Guang-Qian
GQ
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D000077553:Edaravone; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D008565:Membrane Proteins; D012333:RNA, Messenger; C486557:Ern2 protein, rat; D017346:Protein Serine-Threonine Kinases; D000077553:Edaravone; D000983:Antipyrine