Cerebral ischemic tolerance induced by 3-nitropropionic acid is associated with increased expression of erythropoietin in rats.
To examine the changes in erythropoietin (Epo) protein and its mRNA expression in rat brain subjected to focal ischemia and possible mechanism of the preconditioning of mitochondrial toxin 3-nitropropionic acid (3-NPA), rats were administrated either vehicle or 3-NPA at a dose of 20 mg/kg, intraperitoneally (ip), 3 days prior to a 2-h middle cerebral artery occlusion followed by 24-h reperfusion. Infarct volumes were measured by using 2, 3, 5 triphenylte trazolinm chloride (TTC) staining, and Epo protein and its mRNA levels were assessed by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Our results showed that after reperfusion, Epo was found to be expressed extensively in the rat brain. It was most apparent in the basal nuclei and hippocampus, and was, to some extent, present in cortex. Preconditioning with 3-NPA caused a reduction in infarct volume. The expression of both Epo protein and mRNA increased significantly in the different brain areas in the 3-NPA pretreated group as compared with the non-pretreated ischemia model group. These results suggested that preconditioning with low dose 3-NPA could induce ischemic tolerance and neuro-protective effects by increasing the Epo expression in the ischemic and ischemia-related areas.
Zhu
Hongcan
H
Department of Neurology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
Sun
Shenggang
S
Li
Hongge
H
Xu
Yuming
Y
D000818:Animals; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology*; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D009574:Nitro Compounds / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D004921:Erythropoietin; C015392:3-nitropropionic acid