EFFECTS OF ERYTHROPOIETIN ON NITRIC OXIDE SYNTHASE TYPES IN THE HIPPOCAMPUS AND FRONTAL CORTEX IN PTZ-INDUCED SEIZURES IN RATS

Year 2019, , 107 - 115, 19.06.2019

Ayşegül Kapucu

https://doi.org/10.26650/IUITFD.416053

Abstract

Objective: Nitric oxide, an important mediator in the dysfunctions of learning-memory and epileptogenesis, is formed by nitric oxide synthase (NOS) in neuronal cells in many areas of the brain, primarily the hippocampus. It is has been shown that erythropoietin (EPO) has neuroprotective and antiepileptic effects. The aims of this study was to investigate the effects of EPO pre-treatment on convulsions and NOS species in the hippocampus and frontal cortex in pentylenetetrazole (PTZ)-induced generalized seizure model. Material and Method: Forty adult male Wistar albino rats were divided into four groups: Control-saline; PTZ-single dose 60 mg/ kg; EPO-3000 IU/kg; and EPO+PTZ- EPO pretreatment 24 hours before PTZ administration. After the administration of PTZ, the seizure severity (stage) was observed and scored. The levels of neuronal NOS (nNOS), endothelial NOS (eNOS), inducible NOS (iNOS) levels in the plasma, hippocampus and frontal cortex specimens of animals and expressions of NOS species in the hippocampus tissues were examined. Results: EPO pretreatment decreased seizure stage (p<0.01). EPO administration alone reduced nNOS levels in plasma (p<0.001), frontal cortex (p<0.05), hippocampus (p<0.001). Hipocampus nNOS level and expression increased in the EPO+PTZ group compared to the PTZ group (p<0.001). eNOS (p<0.01) and iNOS (p<0.05) levels of hippocampus decreased in the PTZ group; EPO pretreatment before PTZ application improved nNOS level. Conclusion: The EPO pre-treatment demonstrated anticonvulsive effects by increasing eNOS and nNOS levels. EPO pre-treatment can reduce the hyperexcitability of neurons by increasing blood flow in the hypocampus via eNOS. In addition, EPO may contribute to its anticonvulsive effects by inhibiting the decrease of eNOS and nNOS by acting as antioxidant.

Keywords

nitric oxide synthase, hippocampus, seizure, erythropoietin, seizure

SIÇANLARDA PTZ-KAYNAKLI NÖBETLERDE ERİTROPOİETİNİN HİPOKAMPUS VE FRONTAL KORTEKSTE NİTRİK OKSİT SENTAZ TÜRLERİ ÜZERİNE ETKİLERİ

Abstract

Amaç: Öğrenme-hafıza bozukluklarında ve epileptogenezde önemli bir medyatör olan nitrik oksit, hipokampus başta olmak üzere beynin birçok bölgesinde nöronal hücrelerde nitrik oksit sentaz (NOS) tarafından oluşturulur. Eritropoietin (EPO)’nun nöroprotektif ve antiepileptik etkileri olduğu gösterilmiştir. EPO ön-uygulamasının, pentilentetrazol (PTZ) ile indüklenen jeneralize nöbet modelinde konvulsiyonlar ve hipokampus ve frontal kortekste NOS türleri üzerine etkilerini araştırmayı amaçladık. Gereç ve Yöntem: Wistar albino 40 erkek sıçan 4 gruba ayrıldı: kontrol, PTZ-tek doz 60 mg/kg; EPO-3000 IU/kg; EPO+PTZ grubu-PTZ uygulanmasından 24 saat önce EPO ön-uygulaması yapılan grup. PTZ uygulamasından sonra, nöbet şiddeti gözlendi ve skorlandı. Sıçanların plazma, hipokampus ve frontal korteks örneklerinde nöronal NOS (nNOS), endotelyal NOS (eNOS), indüklenebilir NOS (iNOS) düzeyleri ve hipokampusde NOS türlerinin anlatımları değerlendirildi. Bulgular: EPO ön-uygulaması nöbet şiddetini azalttı. Tek başına EPO uygulaması nNOS düzeyini plazma (p<0,001), frontal korteks (p<0,05) ve hipokampus (p<0,001) örneklerinde azalttı. Hipokampus nNOS düzeyi ve anlatımı, EPO+PTZ grubunda, PTZ grubuna göre arttı (p<0,001). PTZ uygulamasıyla hipokampusde eNOS (p<0,01) ve iNOS (p<0,05) azalırken; EPO ön-uygulamasıyla kontrole yakın olduğu gözlendi. Sonuç: EPO ön-uygulaması antikonvulsif etkilerini, eNOS ve nNOS düzeylerini artırarak gösterdi. EPO ön-uygulaması, eNOS aracılığıyla hipokapusde kan akımını artırarak, nöronların hipereksitabilitesini azaltabilir. Ayrıca EPO, antioksidan görevi görerek eNOS ve nNOS’un azalmasını engelleyerek antikonvulzif etkilerine katkıda bulunabilir.

Keywords

eritropoietin, nitrik oksit sentaz, hipokampus, nöbet

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