The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform
Heidrun Potschka - One of the best experts on this subject based on the ideXlab platform.
-
epileptogenesis associated alterations of heat shock protein 70 in a rat post Status Epilepticus Model
Neuroscience, 2019Co-Authors: Fabio Gualtieri, Evalotta Von Ruden, Isabel Seiffert, Marta Nowakowska, Heidrun PotschkaAbstract:Temporal lobe epilepsy is triggered by an initial insult, such as Status Epilepticus, that initiates the process of epilepsy development. Heat shock protein 70 (Hsp70) is a ubiquitously expressed molecular chaperone, involved in the inflammatory response that is upregulated after Status Epilepticus. Hsp70 has been described as an endogenous intracellular ligand of Toll-like receptor 4. It is released from damaged or necrotic tissue and by activated immune cells after an inflammatory event. So far, the time course and the pattern of epileptogenesis-associated alterations in Hsp70 expression have not been described in detail. Thus, we investigated immunohistochemical expression of Hsp70 in hippocampus, parahippocampal cortex, parietal cortex, amygdala, and thalamus following Status Epilepticus in a rat Model of temporal lobe epilepsy. The impact of Status Epilepticus on Hsp70 expression varied during different phases of epileptogenesis, displaying a stronger effect in the early post-insult phase, a milder and more localized effect in the latency phase and no relevant effect in the chronic phase. Cellular-level characterization revealed that Hsp70 colocalized with the neuronal marker NeuN and with Toll-like receptor 4. No colocalization with the astrocytic marker GFAP or the microglia marker Iba1 was found. The intense neuronal Hsp70 upregulation during the early post-insult phase might contribute to the onset of excessive inflammation triggering molecular and cellular reorganization and generation of a hyperexcitable epileptic network. Therefore, development of multi-targeting strategies aiming at prevention of epileptogenesis should consider Hsp70 modulation in the early days following an epileptogenic insult.
-
toward evidence based severity assessment in rat Models with repeated seizures iii electrical post Status Epilepticus Model
Epilepsia, 2019Co-Authors: Ines Koska, Roelof Maarten Van Dijk, Isabel Seiffert, Valentina Di Liberto, Christina Moller, Rupert Palme, Rainer Hellweg, Heidrun PotschkaAbstract:Objective Ethical approval of experiments in chronic epilepsy Models requires a careful balancing of the expected gain-in-knowledge with the level of distress. Thus recommendations for evidence-based severity assessment and classification are urgently needed for preclinical epilepsy research. Methods Therefore, we have completed a comprehensive analysis of alterations in behavioral, biochemical, and physiological parameters in a rat electrical post-Status Epilepticus Model. Selected parameters were repeatedly analyzed during different experimental phases to obtain information about the level of distress throughout the course of the Model. Results Behavioral patterns comprised an increase in activity along with a reduction in risk assessment behavior, active social interaction, saccharin preference as well as nonessential, but evolutionary-determined behavior such as nest building and burrowing. Among the biochemical parameters, fecal corticosterone metabolites proved to be increased in different phases of the experiment. In the early post-insult phase, this increase was reflected by elevated serum corticosterone concentrations. Telemetric recordings demonstrated increases in home cage activity and heart rate in selected experimental phases but argued against relevant changes in heart rate variability. Comparison between animals with tethered or telemetric recordings including a principal component analysis revealed differences between both groups. Significance The present findings further confirm that burrowing behavior and saccharin preference might serve as valid parameters for severity assessment in chronic epilepsy Models. Considering the course of alterations providing evidence for a more pronounced level of distress in the early phase following Status Epilepticus (SE), we suggest a classification of the electrical post-SE Model as severe. This suggestion may serve as a guidance for laboratory-specific evaluations. Comparison between data from animals with tethered and telemetric recordings indicated an impact of the mode of recordings. However, further research is necessary to analyze the validity of telemetry as a putative refinement measure.
-
minocycline fails to exert antiepileptogenic effects in a rat Status Epilepticus Model
European Journal of Pharmacology, 2016Co-Authors: Vera Russmann, J Goc, Katharina Boes, Tanja Ongerth, Josephine D Salvamoser, Claudia Siegl, Heidrun PotschkaAbstract:The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced Status Epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of Status Epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-Status Epilepticus Model. The typical Status Epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental Model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies.
-
microglial ros production in an electrical rat post Status Epilepticus Model of epileptogenesis
Neuroscience Letters, 2015Co-Authors: Maruja L Rettenbeck, Evalotta Von Ruden, Silvia Bienas, Regina Carlson, Veronika M Stein, Andrea Tipold, Heidrun PotschkaAbstract:Abstract Reactive oxygen species and inflammatory signaling have been identified as pivotal pathophysiological factors contributing to epileptogenesis. Considering the development of combined anti-inflammatory and antioxidant treatment strategies with antiepileptogenic potential, a characterization of the time course of microglial reactive oxygen species generation during epileptogenesis is of major interest. Thus, we isolated microglia cells and analyzed the generation of reactive oxygen species by flow cytometric analysis in an electrical rat post-Status Epilepticus Model. Two days post Status Epilepticus, a large-sized cell cluster exhibited a pronounced response with excessive production of reactive oxygen species upon stimulation with phorbol-myristate-acetate. Neither in the latency phase nor in the chronic phase with spontaneous seizures a comparable cell population with induction of reactive oxygen species was identified. We were able to demonstrate in the electrical rat post-Status-Epilepticus Model, that microglial ROS generation reaches a peak after the initial insult, is only marginally increased in the latency phase, and returns to control levels during the chronic epileptic phase. The data suggest that a combination of anti-inflammatory and radical scavenging approaches might only be beneficial during a short time window after an epileptogenic brain insult.
-
The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-Status Epilepticus Model.
Neuroscience letters, 2013Co-Authors: Vera Russmann, Natalie Seeger, Christina Zellinger, Martin Hadamitzky, Stanislava Pankratova, Hannes Wendt, Elisabeth Bock, Vladimir Berezin, Heidrun PotschkaAbstract:Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-Status Epilepticus Model. Cintrofin prevented long-term alterations in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute Status Epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity. Whereas Status Epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data argue against an antiepileptogenic effect, they indicate a putative disease-modifying impact of Cintrofin.
Vera Russmann - One of the best experts on this subject based on the ideXlab platform.
-
minocycline fails to exert antiepileptogenic effects in a rat Status Epilepticus Model
European Journal of Pharmacology, 2016Co-Authors: Vera Russmann, J Goc, Katharina Boes, Tanja Ongerth, Josephine D Salvamoser, Claudia Siegl, Heidrun PotschkaAbstract:The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced Status Epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of Status Epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-Status Epilepticus Model. The typical Status Epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental Model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies.
-
The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-Status Epilepticus Model.
Neuroscience letters, 2013Co-Authors: Vera Russmann, Natalie Seeger, Christina Zellinger, Martin Hadamitzky, Stanislava Pankratova, Hannes Wendt, Elisabeth Bock, Vladimir Berezin, Heidrun PotschkaAbstract:Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-Status Epilepticus Model. Cintrofin prevented long-term alterations in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute Status Epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity. Whereas Status Epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data argue against an antiepileptogenic effect, they indicate a putative disease-modifying impact of Cintrofin.
-
lacosamide treatment following Status Epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical Status Epilepticus Model
Epilepsia, 2013Co-Authors: Thomas Licko, Vera Russmann, Natalie Seeger, Christina Zellinger, Alain Matagne, Heidrun PotschkaAbstract:Summary Purpose The antiepileptic drug, lacosamide, exerts its therapeutic activity by enhancing slow inactivation of voltage-gated sodium channels. Because putative preventive or disease-modifying effects of drugs may affect epileptogenesis, intrinsic severity, and comorbidities, it is of particular interest to assess the effect of lacosamide on the development of epilepsy and associated cellular alterations. Methods The effect of lacosamide was evaluated in an electrical rat Status Epilepticus (SE) Model with a 24-day treatment phase following induction of SE. The impact of lacosamide on the development of spontaneous seizures based on continuous video–electroencephalography (EEG) monitoring, as well as the impact on neuronal cell loss and alterations in hippocampal neurogenesis, was assessed. Key Findings Neither low-dose nor high-dose lacosamide affected the development of spontaneous seizures. A dose-dependent neuroprotective effect of lacosamide with significant reduction of neuronal cell loss was observed in the hippocampal CA1 region, as well as in the piriform cortex. In addition, lacosamide attenuated the impact of SE on the rate of hippocampal cell neurogenesis. Moreover, lacosamide prevented a significant rise in the number of persistent basal dendrites. Significance Our data do not support an antiepileptogenic effect of lacosamide. However, because lacosamide reduced SE-associated cellular alterations, it would be of interest to determine whether these effects indicate a putative disease-modifying effect of lacosamide in future studies.
-
the erythropoietin derived peptide mimetic phbsp affects cellular and cognitive consequences in a rat post Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract:Summary Purpose: 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. Key Findings: 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. Significance: 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.
-
The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post–Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract: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. 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. 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. 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. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Cristiane D. Gil - One of the best experts on this subject based on the ideXlab platform.
-
annexin a1 derived peptide ac2 26 in a pilocarpine induced Status Epilepticus Model anti inflammatory and neuroprotective effects
Journal of Neuroinflammation, 2019Co-Authors: Alexandre D. Gimenes, Bruna F. D. Andrade, José Victor P. Pinotti, Sonia M. Oliani, Cristiane D. Gil, Orfa Y GalvisalonsoAbstract:Background The inflammatory process has been described as a crucial mechanism in the pathophysiology of temporal lobe epilepsy. The anti-inflammatory protein annexin A1 (ANXA1) represents an interesting target in the regulation of neuroinflammation through the inhibition of leukocyte transmigration and the release of proinflammatory mediators. In this study, the role of the ANXA1-derived peptide Ac2-26 in an experimental Model of Status Epilepticus (SE) was evaluated.
-
Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced Status Epilepticus Model: anti-inflammatory and neuroprotective effects
BMC, 2019Co-Authors: Alexandre D. Gimenes, Bruna F. D. Andrade, José Victor P. Pinotti, Sonia M. Oliani, Orfa Y. Galvis-alonso, Cristiane D. GilAbstract:Abstract Background The inflammatory process has been described as a crucial mechanism in the pathophysiology of temporal lobe epilepsy. The anti-inflammatory protein annexin A1 (ANXA1) represents an interesting target in the regulation of neuroinflammation through the inhibition of leukocyte transmigration and the release of proinflammatory mediators. In this study, the role of the ANXA1-derived peptide Ac2-26 in an experimental Model of Status Epilepticus (SE) was evaluated. Methods Male Wistar rats were divided into Naive, Sham, SE and SE+Ac2-26 groups, and SE was induced by intrahippocampal injection of pilocarpine. In Sham animals, saline was applied into the hippocampus, and Naive rats were only handled. Three doses of Ac2-26 (1 mg/kg) were administered intraperitoneally (i.p.) after 2, 8 and 14 h of SE induction. Finally, 24 h after the experiment-onset, rats were euthanized for analyses of neuronal lesion and inflammation. Results Pilocarpine induced generalised SE in all animals, causing neuronal damage, and systemic treatment with Ac2-26 decreased neuronal degeneration and albumin levels in the hippocampus. Also, both SE groups showed an intense influx of microglia, which was corroborated by high levels of ionised calcium binding adaptor molecule 1(Iba-1) and monocyte chemoattractant protein-1 (MCP-1) in the hippocampus. Ac2-26 reduced the astrocyte marker (glial fibrillary acidic protein; GFAP) levels, as well as interleukin-1β (IL-1β), interleukin-6 (IL-6) and growth-regulated alpha protein (GRO/KC). These effects of the peptide were associated with the modulation of the levels of formyl peptide receptor 2, a G-protein-coupled receptor that binds to Ac2-26, and the phosphorylated extracellular signal-regulated kinase (ERK) in the hippocampal neurons. Conclusions The data suggest a neuroprotective effect of Ac2-26 in the epileptogenic processes through downregulation of inflammatory mediators and neuronal loss
Natalie Seeger - One of the best experts on this subject based on the ideXlab platform.
-
The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-Status Epilepticus Model.
Neuroscience letters, 2013Co-Authors: Vera Russmann, Natalie Seeger, Christina Zellinger, Martin Hadamitzky, Stanislava Pankratova, Hannes Wendt, Elisabeth Bock, Vladimir Berezin, Heidrun PotschkaAbstract:Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-Status Epilepticus Model. Cintrofin prevented long-term alterations in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute Status Epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity. Whereas Status Epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data argue against an antiepileptogenic effect, they indicate a putative disease-modifying impact of Cintrofin.
-
lacosamide treatment following Status Epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical Status Epilepticus Model
Epilepsia, 2013Co-Authors: Thomas Licko, Vera Russmann, Natalie Seeger, Christina Zellinger, Alain Matagne, Heidrun PotschkaAbstract:Summary Purpose The antiepileptic drug, lacosamide, exerts its therapeutic activity by enhancing slow inactivation of voltage-gated sodium channels. Because putative preventive or disease-modifying effects of drugs may affect epileptogenesis, intrinsic severity, and comorbidities, it is of particular interest to assess the effect of lacosamide on the development of epilepsy and associated cellular alterations. Methods The effect of lacosamide was evaluated in an electrical rat Status Epilepticus (SE) Model with a 24-day treatment phase following induction of SE. The impact of lacosamide on the development of spontaneous seizures based on continuous video–electroencephalography (EEG) monitoring, as well as the impact on neuronal cell loss and alterations in hippocampal neurogenesis, was assessed. Key Findings Neither low-dose nor high-dose lacosamide affected the development of spontaneous seizures. A dose-dependent neuroprotective effect of lacosamide with significant reduction of neuronal cell loss was observed in the hippocampal CA1 region, as well as in the piriform cortex. In addition, lacosamide attenuated the impact of SE on the rate of hippocampal cell neurogenesis. Moreover, lacosamide prevented a significant rise in the number of persistent basal dendrites. Significance Our data do not support an antiepileptogenic effect of lacosamide. However, because lacosamide reduced SE-associated cellular alterations, it would be of interest to determine whether these effects indicate a putative disease-modifying effect of lacosamide in future studies.
-
the erythropoietin derived peptide mimetic phbsp affects cellular and cognitive consequences in a rat post Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract:Summary Purpose: 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. Key Findings: 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. Significance: 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.
-
The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post–Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract: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. 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. 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. 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. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Christina Zellinger - One of the best experts on this subject based on the ideXlab platform.
-
The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-Status Epilepticus Model.
Neuroscience letters, 2013Co-Authors: Vera Russmann, Natalie Seeger, Christina Zellinger, Martin Hadamitzky, Stanislava Pankratova, Hannes Wendt, Elisabeth Bock, Vladimir Berezin, Heidrun PotschkaAbstract:Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-Status Epilepticus Model. Cintrofin prevented long-term alterations in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute Status Epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity. Whereas Status Epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data argue against an antiepileptogenic effect, they indicate a putative disease-modifying impact of Cintrofin.
-
lacosamide treatment following Status Epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical Status Epilepticus Model
Epilepsia, 2013Co-Authors: Thomas Licko, Vera Russmann, Natalie Seeger, Christina Zellinger, Alain Matagne, Heidrun PotschkaAbstract:Summary Purpose The antiepileptic drug, lacosamide, exerts its therapeutic activity by enhancing slow inactivation of voltage-gated sodium channels. Because putative preventive or disease-modifying effects of drugs may affect epileptogenesis, intrinsic severity, and comorbidities, it is of particular interest to assess the effect of lacosamide on the development of epilepsy and associated cellular alterations. Methods The effect of lacosamide was evaluated in an electrical rat Status Epilepticus (SE) Model with a 24-day treatment phase following induction of SE. The impact of lacosamide on the development of spontaneous seizures based on continuous video–electroencephalography (EEG) monitoring, as well as the impact on neuronal cell loss and alterations in hippocampal neurogenesis, was assessed. Key Findings Neither low-dose nor high-dose lacosamide affected the development of spontaneous seizures. A dose-dependent neuroprotective effect of lacosamide with significant reduction of neuronal cell loss was observed in the hippocampal CA1 region, as well as in the piriform cortex. In addition, lacosamide attenuated the impact of SE on the rate of hippocampal cell neurogenesis. Moreover, lacosamide prevented a significant rise in the number of persistent basal dendrites. Significance Our data do not support an antiepileptogenic effect of lacosamide. However, because lacosamide reduced SE-associated cellular alterations, it would be of interest to determine whether these effects indicate a putative disease-modifying effect of lacosamide in future studies.
-
the erythropoietin derived peptide mimetic phbsp affects cellular and cognitive consequences in a rat post Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract:Summary Purpose: 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. Key Findings: 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. Significance: 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.
-
The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post–Status Epilepticus Model
Epilepsia, 2011Co-Authors: Natalie Seeger, Vera Russmann, Christina Zellinger, Hannes Wendt, Ariane Rode, Frank Roloff, Gerd Bicker, Sarah Fischborn, Heidrun PotschkaAbstract: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. 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. 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. 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. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.