Erythropoietin preconditioning suppresses neuronal death following status epilepticus in rats.
Status epilepticus (SE) is a grave condition in which the brain undergoes lasting seizures which can lead to neuronal loss. Our previous study suggested that preconditioning with erythropoietin (Epo) suppressed neuronal apoptosis in hippocampus of rats following SE in vivo by inhibiting caspase-3. In this study, we investigated the mechanisms by which Epo preconditioning may exert its anti-apoptotic effects using a lithium-pilocarpine induced SE model in rats. The effects of Epo on neuronal cell death were evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the role of the Bcl-2 protein family, which have been shown to be anti- (Bcl-2, Bcl-w) or pro- (Bid, Bim) apoptotic, was examined with immunofluorescence. We found Epo preconditioning decreased the total number of TUNEL, Bim and Bid positive cells, but increased the total number of Bcl-w and Bcl-2 positive cells. These results suggest that systemic Epo pretreatment protects neurons in an acute phase of SE and may result in further suppression of neuronal apoptosis in hippocampus by regulating the balance between pro- and anti-apoptotic Bcl-2 family proteins.
Yang
Jun
J
Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Huang
YuanGui
Y
Yu
Xin
X
Sun
Hong
H
Li
YongNan
Y
Deng
YanChun
Y
D000704:Analysis of Variance; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D004921:Erythropoietin / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010862:Pilocarpine; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*
D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D007211:Indoles; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D010862:Pilocarpine; D004921:Erythropoietin; C007293:DAPI