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

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2004
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Wang, Xiaoyang
Zhu, Changlian
Wang, Xinhua
Gerwien, Jens Gammeltoft
Schrattenholz, André
Sandberg, Mats
Blomgren, Klas
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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% O2 for 50 min). EPO (10 U/g body weight ¼ 80 ng/g; n ¼ 24), asialoEPO (80 ng/g; n ¼ 23) or vehicle (phosphate-buffered saline with 0.1% human serum albumin; n ¼ 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.

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570 Biowissenschaften, Biologie
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asialoerythropoietin, erythropoietin, hypoxia, ischemia, neonatal, neuroprotection
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ISO 690WANG, Xiaoyang, Changlian ZHU, Xinhua WANG, Jens Gammeltoft GERWIEN, André SCHRATTENHOLZ, Mats SANDBERG, Marcel LEIST, Klas BLOMGREN, 2004. The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin. In: Journal of Neurochemistry. 2004, 91(4), pp. 900-910. ISSN 0022-3042. eISSN 1471-4159. Available under: doi: 10.1111/j.1471-4159.2004.02769.x
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@article{Wang2004noner-8136,
  year={2004},
  doi={10.1111/j.1471-4159.2004.02769.x},
  title={The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin},
  number={4},
  volume={91},
  issn={0022-3042},
  journal={Journal of Neurochemistry},
  pages={900--910},
  author={Wang, Xiaoyang and Zhu, Changlian and Wang, Xinhua and Gerwien, Jens Gammeltoft and Schrattenholz, André and Sandberg, Mats and Leist, Marcel and Blomgren, Klas}
}
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