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.