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32 results on '"Feja, Malte"'

10. Alpha synuclein processing by MMP-3 – implications for synucleinopathies

Author

Bluhm, Alexandra, primary, Schrempel, Sarah, additional, Moceri, Sandra, additional, Stieler, Jens, additional, Feja, Malte, additional, Schilling, Stephan, additional, Schulze, Anja, additional, von Hörsten, Stephan, additional, Hartlage-Rübsamen, Maike, additional, Richter, Franziska, additional, and Roßner, Steffen, additional

Published
2022
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14. Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies

Author

Gernert, Manuela and Feja, Malte

Subjects
microinfusion, focal epilepsy, lcsh:Pharmacy and materia medica, drug-resistant epilepsy, convection-enhanced delivery, basal ganglia, microinjection, lcsh:RS1-441, Review, temporal lobe epilepsy, intracerebral drug delivery, targeted drug delivery, seizures
Abstract

Epilepsies are common chronic neurological diseases characterized by recurrent unprovoked seizures of central origin. The mainstay of treatment involves symptomatic suppression of seizures with systemically applied antiseizure drugs (ASDs). Systemic pharmacotherapies for epilepsies are facing two main challenges. First, adverse effects from (often life-long) systemic drug treatment are common, and second, about one-third of patients with epilepsy have seizures refractory to systemic pharmacotherapy. Especially the drug resistance in epilepsies remains an unmet clinical need despite the recent introduction of new ASDs. Apart from other hypotheses, epilepsy-induced alterations of the blood-brain barrier (BBB) are thought to prevent ASDs from entering the brain parenchyma in necessary amounts, thereby being involved in causing drug-resistant epilepsy. Although an invasive procedure, bypassing the BBB by targeted intracranial drug delivery is an attractive approach to circumvent BBB-associated drug resistance mechanisms and to lower the risk of systemic and neurologic adverse effects. Additionally, it offers the possibility of reaching higher local drug concentrations in appropriate target regions while minimizing them in other brain or peripheral areas, as well as using otherwise toxic drugs not suitable for systemic administration. In our review, we give an overview of experimental and clinical studies conducted on direct intracranial drug delivery in epilepsies. We also discuss challenges associated with intracranial pharmacotherapy for epilepsies.

Published
2020

17. Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine

Author

Scherf-Clavel, Oliver, primary, Kaczmarek, Edith, additional, Kinzig, Martina, additional, Friedl, Bettina, additional, Feja, Malte, additional, Höhl, Rainer, additional, Nau, Roland, additional, Holzgrabe, Ulrike, additional, Gernert, Manuela, additional, Richter, Franziska, additional, and Sörgel, Fritz, additional

Published
2020
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26. Untersuchung neuronaler Strukturen und Netzwerke bei der Modulation von Entscheidungsfindung und Impulskontrolle anhand temporärer Inaktivierung durch lokale Mikroinfusion des GABAA-Rezeptor-Agonisten Muscimol bei Ratten

Author

Feja, Malte, Koch, Michael, and Dicke, Ursula

Subjects
delay-discounting, nucleus accumbens, impulsivity, ddc:500, T-maze, five-choice serial reaction time task, 500 Science, ventral medial prefrontal cortex, frontostriatal system
Abstract

Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control.

Published
2014

30. Investigation of neuronal structures and networks on the modulation of decision-making and impulse control by temporary inactivation via local microinfusion of the GABAA receptor agonist muscimol in rats

Author

Feja, Malte and Feja, Malte

Abstract

Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control.

31. Investigation of neuronal structures and networks on the modulation of decision-making and impulse control by temporary inactivation via local microinfusion of the GABAA receptor agonist muscimol in rats

Author

Feja, Malte and Feja, Malte

Abstract

Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control.

32. Investigation of neuronal structures and networks on the modulation of decision-making and impulse control by temporary inactivation via local microinfusion of the GABAA receptor agonist muscimol in rats

Author

Feja, Malte and Feja, Malte

Abstract

Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control.

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