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

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