The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin
The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin
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Date
2004
Authors
Wang, Xiaoyang
Zhu, Changlian
Wang, Xinhua
Gerwien, Jens Gammeltoft
Schrattenholz, André
Sandberg, Mats
Blomgren, Klas
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Journal of Neurochemistry ; 91 (2004), 4. - pp. 900-910. - ISSN 0022-3042. - eISSN 1471-4159
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% 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 Biosciences, Biology
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asialoerythropoietin,erythropoietin,hypoxia,ischemia,neonatal,neuroprotection
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WANG, 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. 91(4), pp. 900-910. ISSN 0022-3042. eISSN 1471-4159. Available under: doi: 10.1111/j.1471-4159.2004.02769.xBibTex
@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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