Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia

• Published in: Neuroscience letters 2005-10, Vol.387 (1), p.5-10
• Main Authors: Yu, Yue-Ping, Xu, Qiu-Qin, Zhang, Qi, Zhang, Wei-Ping, Zhang, Li-Hui, Wei, Er-Qing
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Biological and medical sciences; Brain Edema - drug therapy; Brain Edema - physiopathology; Brain Edema - prevention & control; Brain Ischemia - drug therapy; Brain Ischemia - physiopathology; Brain Ischemia - prevention & control; Cerebral Infarction - drug therapy; Cerebral Infarction - physiopathology; Cerebral Infarction - prevention & control; Cerebral ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Erythropoietin - administration & dosage; Fundamental and applied biological sciences. Psychology; Humans; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - physiopathology; Intranasal delivery; Male; Medical sciences; Nerve Degeneration - drug therapy; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neurology; Neuroprotection; Neuroprotective Agents - administration & dosage; Rats; Rats, Sprague-Dawley; Recombinant human erythropoietin; Recombinant Proteins; Recovery of Function - drug effects; Recovery of Function - physiology; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2005.07.008

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 1 h 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.