Erythropoietin attenuates brain injury, subventricular zone expansion, and sensorimotor deficits in hypoxic-ischemic neonatal rats.
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.
Kim
Sung Shin
SS
Department of Pediatrics, Soonchunhyang University College of Medicine, Bucheon Hospital, Buchoen, Korea.
Lee
Kyung-Hoon
KH
Sung
Dong Kyung
DK
Shim
Jae Won
JW
Kim
Myo Jing
MJ
Jeon
Ga Won
GW
Chang
Yun Sil
YS
Park
Won Soon
WS
D000818:Animals; D000831:Animals, Newborn; D017536:Carotid Artery, Common; D002552:Cerebral Ventricles / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology*; D008026:Ligation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000187:drug effects
D011994:Recombinant Proteins; D004921:Erythropoietin