Experimentelle Epilepsieforschung

Im Vordergrund steht die Untersuchung der Prozesse, die für die Entstehung, die Progression und die Pharmakoresistenz von Epilepsien und ihren Komorbiditäten bei Mensch und Tier verantwortlich sind. Das Ziel ist, Ansatzpunkte für bessere pharmakotherapeutische Strategien zur Verhinderung und Behandlung von Epilepsien und ihren Komorbiditäten zu etablieren. Hierfür werden vor allem Tiermodelle (Maus, Ratte) eingesetzt, an denen die genannten Prozesse mit Methoden der Zell- und Molekularbiologie sowie Neurophysiologie, Neurochemie und Verhaltensbiologie untersucht werden.

Die Forschung der AG Löscher wird von der EU (EPITARGET-Konsortium), der DFG und der Epilepsy Foundation of America gefördert.

C.V.

Wolfgang Löscher

Wolfgang Löscher is a Professor at the Department of Pharmacology, Toxicology and Pharmacy at the University of Veterinary Medicine Hannover, as well as Head of the Center for Systems Neuroscience in Hannover, Germany. He was born in Berlin, Germany, and graduated from the Free University of Berlin with a degree in Veterinary Medicine. He pursued postgraduate training and specialization in Pharmacology, particularly Neuropharmacology and Toxicology in Germany, Denmark, and the United States and holds board certifications in these specialties. He has held posts in academic institutions and the pharmaceutical industry and was appointed as the Director of the Department of Pharmacology in Hannover in 1987, a position that he held for over 30 years. His research interests are in the pharmacology of the brain, including the pharmacology of antiseizure medications, the mechanisms of drug resistance in epilepsy, and the pathophysiology of acquired epilepsies to find new targets for preventive treatment. His many cooperations with the pharmaceutical industry have fostered the development of new antiseizure medications such as levetiracetam (the first blockbuster in epilepsy therapy) and imepitoin (the first therapy developed for canine epilepsy). He has been a founding and managing editor of the journal Epilepsy Research and serves on the editorial board of several scientific journals. He has over 600 refereed publications and an h-index of 92. He has obtained several awards for his research, including the Epilepsy Research Award for Outstanding Contributions to the Pharmacology of Antiepileptic Drugs of the International League against Epilepsy (ILAE) in 2001, the American Epilepsy Society’s Epilepsy Research Award for Basic Science Research in 2006, the Ambassador for Epilepsy Award of the ILAE and IBE in 2011, the European Epileptology Award of the ILAE/CEA in 2014, and the Lifetime Accelerator Award of the Epilepsy Foundation of America in 2018. In 2021, he was identified as one of the world’s most influential researchers by ClarivateTM (Philadelphia).  Since 2000, Löscher is elected member of the German National Academy of Sciences Leopoldina, which is the oldest continuously existing academy of natural sciences and medicine in the world.

 

 

Repräsentative Publikationen (von >600)

Debski, K. J., N. Ceglia, A. Ghestem, A. I. Ivanov, G. E. Brancati, S. Bröer, A. M. Bot, J. A.
Müller, S. Schoch, A. Becker, W. Löscher, M. Guye, P. Sassone-Corsi, K. Lukasiuk, P. Baldi, and C. Bernard: The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy. Science Adv., 6, eaat5979, 2020.

Galovic, M., I. Baudracco, E. Wright-Goff, G. Pillajo, P. Nachev, B. Wandschneider, F. Woermann, P. Thompson, S. Baxendale, A. W. McEvoy, M. Nowell, M. Mancini, S. B. Vos, G. P. Winston, R. Sparks, F. Prados, A. Miserocchi, J. de Tisi, L. A. Van Graan, R. Rodionov, C. Wu, M. Alizadeh, L. Kozlowski, A. D. Sharan, L. G. Kini, K. A. Davis, B. Litt, S. Ourselin, S. L. Moshe, J. W. A. Sander, W. Löscher, J. S. Duncan, and M. J. Koepp: Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy. JAMA Neurol., 76, 690-700, 2019.

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 (PNAS) 115, E9590-E9599, 2018.

Käufer, C., C. Chhatbar, S. Bröer, I. Waltl, L. Ghita, 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 (PNAS) 115, E8929-E8938, 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. Käufer, 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.

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.
 
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.

Pitkänen, A., W. Löscher, A. Vezzani, A. J. Becker, M. Simonato, K. Lukasiuk, O. Gröhn, J. P. Bankstahl, A. Friedman, E. Aronica, J. A. Gorter, T. Ravizza, S. M. Sisodiya, M. Kokaia, and H. Beck: Advances in the development of biomarkers for epilepsy. Lancet Neurol. 15, 843-856, 2016.

Baumgärtner, W. and W. Löscher: Re-emergence of neuroinfectiology. Acta Neuropathol. 131, 155-158, 2016.

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.

Ridder, D. A., J. Wenzel, K. Muller, K. Tollner, X. K. Tong, J. C. Assmann, S. Stroobants, T. Weber, C. Niturad, L. Fischer, B. Lembrich, H. Wolburg, M. Grand'Maison, P. Papadopoulos, E. Korpos, F. Truchetet, D. Rades, L. M. Sorokin, M. Schmidt-Supprian, B. J. Bedell, M. Pasparakis, D. Balschun, R. D'Hooge, W. Löscher, E. Hamel, and M. Schwaninger: Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J.Exp.Med. 212, 1529-1549, 2015.

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.  

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

Töllner, K., S. Wolf, W. Löscher, and M. Gernert: The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: a new mechanism of pharmacoresistance. J. Neurosci. 31, 16423-16434, 2011.  

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.

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.  

Löscher, W., M. Gernert, and U. Heinemann: Cell and gene therapies in epilepsy--promising avenues or blind alleys? Trends Neurosci. 31, 62-73, 2008.

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.

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. and H. Potschka: Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog.Neurobiol. 76, 22-76, 2005.

Rogawski, M. A. and W. Löscher: The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nature Med. 10, 685-692, 2004.  

Rogawski, M. A. and W. Löscher: The neurobiology of antiepileptic drugs. Nature Rev. Neurosci. 5, 553-564, 2004.

Fedrowitz, M., K. Kamino, and W. Löscher: Significant differences in the effects of magnetic field exposure on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of Sprague-Dawley rats. Cancer Res. 64, 243-251, 2004.

Löscher, W. Current status and future directions in the pharmacotherapy of epilepsy. Trends Pharmacol. Sci. 23, 113-8, 2002.

Fedrowitz, M., J. Westermann, and W. Löscher: Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats. Cancer Res. 62:1356-63, 2002.

Löscher, W.: Valproate: A reappraisal of its pharmacodynamic properties and mechanisms of
action. Progr. Neurobiol. 58:31-59, 1999.

Thun-Battersby, S., M. Mevissen, and W. Löscher Exposure of Sprague-Dawley rats to a 50-Hertz, 100-µTesla magnetic field for 27 weeks facilitates mammary tumorigenesis in the 7,12-dimethylbenz[a]anthracene model of breast cancer. Cancer Res. 59:3627-3633, 1999.

Richter, A. and W. Löscher: Pathophysiology of idiopathic dystonia: Findings from genetic animal models. Prog. Neurobiol. 54, 633-677, 1998.

Löscher, W.: Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy. Prog. Neurobiol. 54, 721-741, 1998.

Löscher, W.: Animal models of intractable epilepsy. Prog. Neurobiol. 53, 239-258, 1997.

Löscher, W. and U. Ebert: The role of the piriform cortex in kindling. Progr. Neurobiol. 50, 427-481, 1996.

Löscher, W., L. Gram and H. Stefan: Plasma GABA and seizure control with vigabatrin. Lancet 341, 117, 1993.

Löscher, W. and D. Hönack: Responses to NMDA receptor antagonists altered by epileptogenesis. Trends pharmacol. Sci. 12, 52, 1991.

Löscher, W. and C. Rundfeldt: Intermittent flumazenil and benzodiazepine tolerance: discouraging findings in rats. Lancet i, 1386-1387, 1989.

Löscher, W. and H. Siemes: Valproic acid increases γ-aminobutyric acid in CSF of epileptic children. Lancet ii, 225, 1984.