title: Impact of the erythropoietin-derived peptide mimetic Epotris on the histopathological consequences of status epilepticus.
abstract: The design of peptide mimetics offers interesting opportunities to selectively include beneficial and exclude undesirable effects of a parent molecule. Epotris represents a novel erythropoietin mimetic, which lacks an erythropoietic activity. The present study evaluates the potential of this peptide to interfere with the histopathological consequences of electrical-induced status epilepticus in rats. The peptide attenuated status epilepticus-associated expansion of the neuronal progenitor cell population in a significant manner. Moreover, Epotris affected the number of persistent basal dendrites exhibited by neuronal progenitor cells. In contrast, hippocampal cell loss remained unaffected by administration of this peptide mimetic. Status epilepticus resulted in obvious microglial activation in different brain regions involved in seizure generation and spread. Epotris diminished the microglial response caused by prolonged seizure activity in the thalamus but not in other brain regions. The study renders support that the Epotris' sequences from binding site 2 in helix C of Epo play a role in receptor interaction and cytokine function. In addition, the data demonstrate that Epotris can exert limited in vivo effects on the cellular consequences of prolonged seizure activity. When considering further testing it should be taken in mind that Epotris administration only attenuated selected cellular consequences of status epilepticus and did not completely prevent cellular alterations.
authors: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Koeniginstr. 16, D-80539 Munich, Germany.
authors: Christina
authors: C
authors: Zellinger
authors: Natalie
authors: N
authors: Seeger
authors: Martin
authors: M
authors: Hadamitzky
authors: Sarah
authors: S
authors: Fischborn
authors: Vera
authors: V
authors: Russmann
authors: Hannes
authors: H
authors: Wendt
authors: Stanislava
authors: S
authors: Pankratova
authors: Elisabeth
authors: E
authors: Bock
authors: Vladimir
authors: V
authors: Berezin
authors: Heidrun
authors: H
authors: Potschka
mesh_terms: D000818:Animals; D000089622:Doublecortin Domain Proteins; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018716:Molecular Mimicry; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C552536:epotris; D004921:Erythropoietin