Effect of continuous infusion of asialoerythropoietin on short-term changes in infarct volume, penumbra apoptosis and behaviour following middle cerebral artery occlusion in rats.
1. Asialoerythropoietin (aEPO), a derivative of cytokine erythropoietin, has been shown to have neuroprotective effects without haematological complications when administered in single or repeated doses. The present study examines our hypothesis that aEPO may provide neuroprotection against programmed apoptotic cell death when administered in a continuous low dose. 2. Focal cerebral ischaemia was introduced by occlusion of the middle cerebral artery using a surgically placed intraluminal filament in young male Sprague Dawley rats (9 weeks old). After 90 min ischaemia, reperfusion was established by filament removal. Both study and control groups had implanted osmotic minipumps through which they received either aEPO (1 microL/h; 20 microg/kg per 24 h) or normal saline (1 microL/h) for 4 days. On Day 4, infarct volume, the number of apoptotic cells and concentrations of activated caspase 3 and 9 were evaluated in the penumbra region. 3. Asialoerythropoietin was detected in the cerebrospinal fluid of the study group, whereas none was detected in the control group. Although there were no significant changes in haematocrit levels or behaviour scores (on Days 1 and 4) between the study and control groups, aEPO administration significantly reduced infarct volume in the study group compared with the control group (168 +/- 19 vs 249 +/- 28 mm(3), respectively; P < 0.05). 4. The number of terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL)-positive cells and the concentration of activated caspase 3 and 9 in the penumbra region were significantly lower in the study group compared with the control group. 5. In conclusion, our data suggest that aEPO provides a short-term, possibly histological, protection in young adult male rats when administered immediately after reperfusion.
Price
Chrystal D
CD
Department of Anaesthesiology and Critical Care Medicine, University of South Florida, Tampa, Florida, USA.
Yang
Zhongjin
Z
Karlnoski
Rachel
R
Kumar
Dipak
D
Chaparro
Raphael
R
Camporesi
Enrico M
EM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001212:Asialoglycoproteins / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000188:drug therapy; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001212:Asialoglycoproteins; D018696:Neuroprotective Agents; C500605:asialoerythropoietin; D004921:Erythropoietin; D053148:Caspase 3; D053453:Caspase 9