TY - JOUR
T1 - Impact of the erythropoietin-derived peptide mimetic Epotris on the histopathological consequences of status epilepticus
AU - Zellinger, Christina
AU - Seeger, Natalie
AU - Hadamitzky, Martin
AU - Fischborn, Sarah
AU - Russmann, Vera
AU - Wendt, Hannes
AU - Pankratova, Stanislava
AU - Bock, Elisabeth
AU - Berezin, Vladimir
AU - Potschka, Heidrun
N1 - Copyright © 2011 Elsevier B.V. All rights reserved.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.eplepsyres.2011.06.009
DO - 10.1016/j.eplepsyres.2011.06.009
M3 - Journal article
C2 - 21741213
SN - 0920-1211
JO - Epilepsy Research
JF - Epilepsy Research
ER -