Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia.
Erythropoietin (EPO) is a hematopoietic growth factor with tissue-protective properties, and can protect animals from cerebral ischemic injury. However, the central nervous effects of EPO as a glycoprotein is limited by the potential complication resulted from its erythropoietic activity and the problem of the penetration through blood-brain barrier (BBB). To avoid these limitations, in this study we administered recombinant human EPO (rhEPO) intranasally (i.n.) to evaluate its neuroprotective effect in the rats with focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). We found that rhEPO i.n. at doses of 4.8, 12 and 24 U (administered 10 min after MCAO and 1h after reperfusion) reduced infarct volume, brain swelling and cell damage in the ischemic hemispheres, and improved behavioral dysfunction 24 h after cerebral ischemia. Intraperitoneal rhEPO (5000 U/kg) also showed the protective effect, but the heat-inactivated rhEPO did not show any effect. Thus, intranasal administration of relatively small doses of rhEPO protects rats from acute injury after focal cerebral ischemia, suggesting that intranasal rhEPO may be a more effective and safer administration route for treatments of ischemic or other brain diseases.
Yu
Yue-Ping
YP
Department of Pharmacology, School of Medicine, Zhejiang University, 353, Yan An Road, Hangzhou 31003, PR China.
Xu
Qiu-Qin
QQ
Zhang
Qi
Q
Zhang
Wei-Ping
WP
Zhang
Li-Hui
LH
Wei
Er-Qing
EQ
D000281:Administration, Intranasal; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin