title: The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post-status epilepticus model.
abstract: OBJECTIVE
  The selection of a minimal active sequence of erythropoietin allowed the design of peptide mimetics that exert beneficial effects in the central nervous system but lack an erythropoietic effect. Erythropoietin has been suggested as a promising therapeutic and prophylactic for epilepsies based on its neuroprotective, neuroregenerative, and antiinflammatory potency. Therefore, it is of particular interest to evaluate whether the nonerythropoietic erythropoietin-derived peptide pHBSP can affect epileptogenesis.
  
  
  METHODS
  In a post-status epilepticus model in rats, we determined the effects of pHBSP and of recombinant human erythropoietin with short-term administration following status epilepticus.
  
  
  RESULTS
  Both pHBSP and erythropoietin further enhanced the status epilepticus-associated increase in hippocampal cell proliferation. Thereby, pHBSP seemed to promote neuronal differentiation and survival resulting in a significant increase in neurogenesis. Neither pHBSP nor erythropoietin affected the number of animals exhibiting spontaneous recurrent seizures as well as the seizure frequency in the chronic phase. In the Morris water maze, pHBSP attenuated cognitive deficits in epileptic animals.
  
  
  CONCLUSIONS
  In conclusion, the helix B-derived erythropoietin peptide pHBSP can modulate the cellular and cognitive consequences of a status epilepticus. The impact of pHBSP on spatial learning might indicate that the peptide allows beneficial effects on epileptogenesis-associated cognitive deficits. However, it needs to be considered that learning deficits were not abolished by pHBSP and that the effects were not observed consistently until the end of the study. Therefore, adjustment of timing, duration, and dose of peptide administration might be necessary to further evaluate the efficacy of pHBSP.
authors: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
authors: Natalie
authors: N
authors: Seeger
authors: Christina
authors: C
authors: Zellinger
authors: Ariane
authors: A
authors: Rode
authors: Frank
authors: F
authors: Roloff
authors: Gerd
authors: G
authors: Bicker
authors: Vera
authors: V
authors: Russmann
authors: Sarah
authors: S
authors: Fischborn
authors: Hannes
authors: H
authors: Wendt
authors: Heidrun
authors: H
authors: Potschka
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004921:Erythropoietin / Q000737:chemistry*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000627:therapeutic use*; D013226:Status Epilepticus / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
chemical_list: D004921:Erythropoietin; C433550:HABP2 protein, human; D012697:Serine Endopeptidases; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine