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The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin.

Författare och institution:
Xiaoyang Wang (Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi); Changlian Zhu (Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi); Xinhua Wang (Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi); Jens Gammeltoft Gerwien (-); Andre Schrattenholz (-); Mats Sandberg (Institutionen för fysiologi och farmakologi, Avdelningen för medicinsk fysik); Marcel Leist (-); Klas Blomgren (Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi & Institutionen för kvinnors och barns hälsa, Avdelningen för pediatrik)
Publicerad i:
Journal of neurochemistry, 91 ( 4 ) s. 900-10
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Recently, erythropoietin (EPO) and the nonerythropoietic derivative asialoEPO have been linked to tissue protection in the nervous system. In this study, we tested their effects in a model of neonatal hypoxia-ischemia (HI) in 7-day-old rats (unilateral carotid ligation and exposure to 7.7% O(2) for 50 min). EPO (10 U/g body weight = 80 ng/g; n = 24), asialoEPO (80 ng/g; n = 23) or vehicle (phosphate-buffered saline with 0.1% human serum albumin; n = 24) was injected intraperitoneally 4 h before HI. Both drugs were protective, as judged by measuring the infarct volumes, neuropathological score and gross morphological score. The infarct volumes were significantly reduced by both EPO (52%) and asialoEPO (55%) treatment, even though the plasma levels of asialoEPO had dropped below the detection limit (1 pm) at the onset of HI, while those of EPO were in the nanomolar range. Thus, a brief trigger by asialoEPO before the insult appears to be sufficient for protection. Proteomics analysis after asialoEPO treatment alone (no HI) revealed at least one differentially up-regulated protein, synaptosome-associated protein of 25 kDa (SNAP-25). Activation (phosphorylation) of ERK was significantly reduced in asialoEPO-treated animals after HI. EPO and the nonerythropoietic asialoEPO both provided significant and equal neuroprotection when administered 4 h prior to HI in 7-day-old rats. The protection might be related to reduced ERK activation and up-regulation of SNAP-25.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Animals, Newborn, Asialoglycoproteins, biosynthesis, blood, pharmacokinetics, therapeutic use, Brain Infarction, pathology, prevention & control, Disease Models, Animal, Erythropoietin, analogs & derivatives, biosynthesis, blood, pharmacokinetics, therapeutic use, Female, Hypoxia-Ischemia, Brain, drug therapy, pathology, Male, Membrane Proteins, metabolism, Nerve Tissue Proteins, metabolism, Proteomics, methods, Rats, Rats, Wistar, Signal Transduction, drug effects, Synaptosomal-Associated Protein 25, Treatment Outcome
Postens nummer:
Posten skapad:
2007-10-31 10:50
Posten ändrad:
2011-01-20 10:00

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