Erythropoietin attenuates white matter damage, proinflammatory cytokine and chemokine induction in developing rat brain after intra-uterine infection.
To investigate the possible ameliorating effect of recombinant human erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine Escherichia coli infection. E. coli was inoculated into uterine cervix of the time-pregnant rats and the control was injected with normal saline. Following maternal E. coli inoculation, the pups received a single intraperitoneal injection of rhEPO at a dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical staining and Western blot analysis for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were performed to assess white matter damage in pup brains at post-natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO treatment (5000 IU/kg body weight) attenuated white matter damage in developing rat brain after intra-uterine E. coli infection. The protein levels of CNPase and NF in pup brains at P7 significantly increased after post-natal rhEPO treatment as compared with the intra-uterine E. coli-treated group. Also, post-natal rhEPO injection markedly attenuated the intra-uterine E. coli infection-induced increases in GFAP protein expression and the mRNA levels of pro-inflammatory cytokines and chemokines. Post-natal EPO administration as a single dose may exert a neuroprotective effect on white matter damage by reducing pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine E. coli infection.
Shen
Ying
Y
Departments of Neonatology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yu
Hui-Min
HM
Yuan
Tian-Ming
TM
Gu
Wei-Zhong
WZ
Wu
Yi-Dong
YD
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology*; D006801:Humans; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D034161:Pelvic Infection / Q000503:physiopathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013997:Time Factors
D018925:Chemokines; D016207:Cytokines; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin