title: Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizures.
abstract: Erythropoietin (EPO) suppresses epileptic seizures, but the mechanism is unclear. The search for novel targets in the therapy of epilepsy has focused recently on brain inflammation since brain inflammation and the associated blood-brain barrier (BBB) damage appears to be an integral part of epilepsy pathophysiology. We examined the effects of EPO on proinflammatory mediators in brain and serum in PTZ-induced generalized seizure model. The inflammation markers (IL-1β, TNF-α, IL-6, IL-10), BBB and neuron damage markers (S100B, Neuron specific enolase; NSE, respectively) in serum and brain of Sprague-Dawley male rats were examined with the ELISA method. Nitric oxide synthase (NOS) isoforms were investigated immunohistochemically in hippocampus. EPO treatment 4 h and 24 h before PTZ administration had diverse effects. EPO treatment 4 h before PTZ administration elongated the seizure latency, decreased the inflammation and damage markers in serum and brain significantly, whereas EPO treatment 24 h before PTZ administration lowered inflammation and damage markers to control levels and decreased the seizure stage. PTZ-induced seizures increased inducible NOS (iNOS) activity and decreased endothelial NOS (eNOS) activity in hippocampus. Both EPO pretreatments reversed these effects. These findings, i.e., decreased iNOS activity and increased eNOS activity by EPO suggest the first time that the favorable effect of EPO pretreatment on inflammatory mediators triggered by PTZ-induced seizures. This can provide further insight into epilepsy treatment and new prophylactic strategies against epilepsy risk.
authors.affiliation: 1Istanbul Research Hospital, Department of Neurology , Samatya, Istanbul , Turkey.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Bahçekapılı
authors.forename: Kadriye
authors.initials: K
authors.lastname: Akgün-Dar
authors.forename: Işıl
authors.initials: I
authors.lastname: Albeniz
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Kapucu
authors.forename: Aslı
authors.initials: A
authors.lastname: Kandil
authors.forename: Orhan
authors.initials: O
authors.lastname: Yağız
authors.forename: Gülay
authors.initials: G
authors.lastname: Üzüm
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D004660:Encephalitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000627:therapeutic use*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D003292:Convulsants; D016207:Cytokines; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D004921:Erythropoietin; D010751:Phosphopyruvate Hydratase; D010433:Pentylenetetrazole
keywords: S100B; erythropoietin; inflammatory cytokines; neuron specific enolase; nitric oxide synthase; pentylenetetrazole-induced seizures