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

• 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.

Nyckelord

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

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