Erythropoietin prevents nitric oxide and cathepsin-mediated neuronal death in focal brain ischemia.
We examined the preventive effect of human recombinant erythropoietin (HrEPO) on nitric oxide (NO)-mediated toxicity to neurons and cysteine protease release into cytoplasm, which is attributed to neuronal death in brain ischemia. Focal cerebral ischemia was induced by permanent occlusion of middle cerebral artery in two sets of rat. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. A group in both set was administered human recombinant erythropoietin (HrEPO). NO content, cathepsins B and L activity increased significantly in the post-ischemic cerebral tissue (p<0.05). HrEPO treatment reduced NO concentration and cathepsin activity to control level (p>0.05). A significant increase in the number of necrotic and apoptotic neurons was observed in the post-ischemic cerebral cortex (p<0.05). HrEPO treatment was markedly lowered both of these (p<0.05). It is concluded that HrEPO prevents neuronal death by protecting neuronal liposomes from NO-mediated toxicity and suppressing the release of cathepsins.
Department of Anatomy, Eskişehir Osmangazi University School of Medicine, 26480 Eskişehir, Turkey. hilmiozden@gmail.com
Hilmi
H
Ozden
Ramazan
R
Durmaz
Güngör
G
Kanbak
Kubilay
K
Uzuner
Erinc
E
Aral
Kazım
K
Kartkaya
Sibel Canbaz
SC
Kabay
Metin Ant
MA
Atasoy
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002401:Cathepsin B / Q000502:physiology*; D056668:Cathepsin L / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D004921:Erythropoietin; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat