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Research

Research of Prof. Löscher´s group

The focus of our research is the investigation of processes leading to the development, progression and therapy resistance of epilepsies and associated comorbidities in humans and animals. The aim is to establish new or improved pharmacological strategies for the prevention of the development or the therapy of acquired epilepsies. For this purpose, various animal models of epilepsies as well as in vitro models are used. Different methods, such as neurochemistry, electrophysiology, molecular biology or behavioral pharmacology are applied in order to characterize the mentioned processes.

The research of the Löscher lab is supported by the European Union (EPITARGET), the Germany Research Foundation (DFG) and The Epilepsy Foundation of America.

Representative publications (of >600)

Original research

 

Volk, H. A. and W. Löscher:

Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures.

Brain, 128, 1358-1368, 2005

 

Brandt, C., M. Nozadze, N. Heuchert, M. Rattka, and W. Löscher:

Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy.

J. Neurosci., 30, 8602-8612, 2010.

 

Bankstahl, J. P., M. Bankstahl, C. Kuntner, J. Stanek, T. Wanek, M. Meier, X. Q. Ding, M. Müller, O. Langer, and W. Löscher:

A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.

J. Neurosci., 31, 8803-8811, 2011.

 

Töllner, K., C. Brandt, M. Töpfer, G. Brunhofer, T. Erker, M. Gabriel, P. W. Feit, J. Lindfors, K. Kaila, and W. Löscher:

A novel prodrug-based strategy to increase effects of bumetanide in epilepsy.

Ann. Neurol., 75, 550-562, 2014.

 

Bar-Klein, G., R. Klee, C. Brandt, M. Bankstahl, P. Bascunana, K. Töllner, H. Dalipaj, J. P. Bankstahl, A. Friedman, and W. Löscher:

Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy.

Ann. Neurol., 80, 896-908, 2016.

 

Dogbevia, G. K., K. Töllner, J. Korbelin, S. Broer, D. A. Ridder, H. Grasshoff, C. Brandt, J. Wenzel, B. K. Straub, M. Trepel, W. Löscher, and M. Schwaninger:

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

Ann. Neurol., 82, 93-104, 2017.

 

Schidlitzki, A., F. Twele, R. Klee, I. Waltl, K. Römermann, S. Broer, S. Meller, I. Gerhauser, V. Rankovic, D. Li, C. Brandt, M. Bankstahl, K. Töllner, and W. Löscher:

A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy.

Sci. Rep., 7, 12191, 2017.

 

Käufer, C., C. Chatbar, S. Bröer, I. Waltl, G. Luca, I. Gerhauser, U. Kalinke, and W. Löscher:

Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures.

Proc.Natl.Acad.Sci.(USA), 115, E8929-E8938, 2018.

 

Noack, A., B. Gericke, M. von Köckritz-Blickwede, A. Menze, S. Noack, I. Gerhauser, F. Osten, H. Y. Naim, and W. Löscher:

A novel mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils.

Proc.Natl.Acad.Sci.(USA), 115, E9590-E9599, 2018.

 

Stanelle-Bertram, S., K. Walendy-Gnirss, T. Speiseder, S. Thiele, I. A. Asante, C. Dreier, N. M. Kouassi, A. Preuss, G. Pilnitz-Stolze, U. Muller, S. Thanisch, M. Richter, R. Scharrenberg, V. Kraus, R. Dork, L. Schau, V. Herder, I. Gerhauser, V. M. Pfankuche, C. Kaufer, I. Waltl, T. Moraes, J. Sellau, S. Hoenow, J. Schmidt-Chanasit, S. Jansen, B. Schattling, H. Ittrich, U. Bartsch, T. Renne, R. Bartenschlager, P. Arck, D. Cadar, M. A. Friese, O. Vapalahti, H. Lotter, S. Benites, L. Rolling, M. Gabriel, W. Baumgärtner, F. Morellini, S. M. Holter, O. Amarie, H. Fuchs, d. A. Hrabe, W. Löscher, d. A. Calderon, and G. Gabriel:

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood.

Nature Microbiol., 3, 1161-1174, 2018.

Reviews

 

Löscher, W. and D. Hönack:

Responses to NMDA receptor antagonists altered by epileptogenesis.

Trends pharmacol. Sci. 12, 52, 1991.

 

Rogawski, M. A. and W. Löscher:

The neurobiology of antiepileptic drugs.

Nature Rev. Neurosci., 5, 553-564, 2004.

 

Rogawski, M. A. and W. Löscher:

The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions.

Nature Med., 10, 685-692, 2004.

 

Löscher, W. and H. Potschka:

Drug resistance in brain diseases and the role of drug efflux transporters.

Nature Rev.Neurosci., 6, 591-602, 2005.

 

Löscher, W., M. Gernert, and U. Heinemann:

Cell and gene therapies in epilepsy--promising avenues or blind alleys?

Trends Neurosci., 31, 62-73, 2008.

 

Löscher, W. and C. Brandt:

Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research.

Pharmacol.Rev., 62, 668-700, 2010.

 

Löscher, W., H. Klitgaard, R. E. Twyman, and D. Schmidt:

New avenues for antiepileptic drug discovery and development.

Nature Rev. Drug Discov., 12, 757-776, 2013.

 

Löscher, W. and D. Schmidt:

Perampanel-new promise for refractory epilepsy?

Nature Rev. Neurol., 8, 661-662, 2012.

 

Vezzani, A., R. S. Fujinami, H. S. White, P. M. Preux, I. Blümcke, J. W. Sander, and W. Löscher:

Infections, inflammation and epilepsy.

Acta Neuropathol., 131, 211-234, 2016.

 

Klein, P., R. Dingledine, E. Aronica, C. Bernard, I. Blümcke, D. Boison, M. J. Brodie, A. R. Brooks-Kayal, J. Engel, Jr., P. A. Forcelli, L. J. Hirsch, R. M. Kaminski, H. Klitgaard, K. Kobow, D. H. Lowenstein, P. L. Pearl, A. Pitkänen, N. Puhakka, M. A. Rogawski, D. Schmidt, M. Sillanpää, R. S. Sloviter, C. Steinhäuser, A. Vezzani, M. C. Walker, and W. Löscher:

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Epilepsia, 59, 37-66, 2018.

 

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