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KMID : 0191120080230030484
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Journal of Korean Medical Science
2008 Volume.23 No. 3 p.484 ~ p.491
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Erythropoietin Attenuates Brain Injury, Subventricular Zone Expansion, and Sensorimotor Deficits in Hypoxic-Ischemic Neonatal Rats
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Kim Shin-Sung
Lee Kyung-Hoon
Sung Dong-Kyung
Shim Jae-Won
Kim Myo-Jing
Jeon Ga-Won
Chang Yun-Sil
Park Won-Soon
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Abstract
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The aim of this study was to investigate the effect of erythropoietin (EPO) on histological
brain injury, subventricular zone (SVZ) expansion, and sensorimotor function
deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old
male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia
control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was
performed in all animals. HI was induced by ligation of the right common carotid
artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3
U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after
insult. At two weeks after insult, animals were challenged with cylinder-rearing test
for evaluating forelimb asymmetry to determine sensorimotor function. All animals
were then sacrificed for volumetric analysis of the cerebral hemispheres and the
SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of
the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of
brains revealed significantly decreased preserved ipsilateral hemispheric volume
and increased ipsilateral SVZ volume compared with the sham-operated animals.
Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral
hemispheric volume along with decreased expansion of ipsilateral SVZ following
HI compared to the saline-treated HI rats. These results support the use of
EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage.
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KEYWORD
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Hypoxia-Ischemia, Brain, Animals, Newborn, Subventricular Zone, Function
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