科研之友
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摘要
Background and purpose: Systemic administration of high-dose recombinant human erythropoietin (rhEPO) is known to attenuate ischemic injury. However, high-dose rhEPO might aggravate ischemic lesions by increasing blood viscosity because of its erythropoietic effects. Asialoerythropoietin (asialoEPO), an EPO derivative with an extremely short plasma half-life, has considerably lesser erythropoietic effect than that of naive EPO. We attempted to determine whether asialoEPO exerts the same neuroprotective effect as naive EPO in a gerbil transient forebrain ischemia model.
Methods: Transient occlusion of both the common carotid arteries was performed in 23 adult gerbils. The drugs (asialoEPO or rhEPO, 10 U/g bodyweight) or phosphate-buffered saline (PBS) were injected intraperitoneally at three times (3 hours before, immediately after, and 24 hours after the ischemic insult). Learning and retention tests were performed on days 6 and 7, respectively, and histological analyses were performed on day 7.
Results: Animals treated with asialoEPO and rhEPO showed significant neurological improvement compared to the PBS-treated animals. The number of viable neurons in the CA1 field of the rhEPO-treated (103.57 +/- 27.90 cells/mm) and asialoEPO-treated (144.99 +/- 34.87 cells/mm) animals was higher than that of the PBS-treated animals (19.53 +/- 3.79 cells/mm). Terminal dinucleotidyltransferase-mediated UTP end labeling-positive cells were significantly lower in the rhEPO-treated (33.40 +/- 8.13 cells/mm) and asialoEPO-treated (29.28 +/- 14.91 cells/mm) animals than in the PBS-treated animals (76.67 +/- 8.14 cells/mm). AsialoEPO treatment did not have any effect on erythropoiesis.
Conclusion: Multiple dosing of asialoEPO, like EPO, could protect the hippocampal CA1 neurons from ischemic damage without affecting erythropoiesis.
- 出版日期2010-11
