Asialoerythropoietin attenuates neuronal cell death in the hippocampal CA1 region after transient forebrain ischemia in a gerbil model

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)...

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Published in:Neurological research (New York) 2010-11, Vol.32 (9), p.957-962
Main Authors: Yamashita, Taro, Nonoguchi, Naosuke, Ikemoto, Toshiyuki, Miyatake, Shin-Ichi, Kuroiwa, Toshihiko
Format: Article
Language:English
Subjects:
Animals
APOPTOSIS
ASIALOERYTHROPOIETIN
Asialoglycoproteins - pharmacology
Avoidance Learning - drug effects
BRAIN ISCHEMIA
CA1 Region, Hippocampal - pathology
Carotid Artery Diseases - complications
Cell Count - methods
Cell Death - drug effects
Chromatography, High Pressure Liquid - methods
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Erythropoietin - analogs & derivatives
Erythropoietin - pharmacology
Erythropoietin - therapeutic use
Gerbillinae
In Situ Nick-End Labeling - methods
Ischemic Attack, Transient - drug therapy
Ischemic Attack, Transient - etiology
Ischemic Attack, Transient - pathology
Ischemic Attack, Transient - physiopathology
Neurons - drug effects
NEUROPROTECTION
Neuroprotective Agents - pharmacology
Prosencephalon - pathology
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Summary: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.
ISSN:0161-6412
1743-1328
DOI:10.1179/016164110X12700393823336