Wolfgang Loscher

Summary

Affiliation: University of Veterinary Medicine
Country: Germany

Publications

  1. ncbi Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Neuropharmacology 69:62-74. 2013
  2. ncbi How theories evolved concerning the mechanism of action of barbiturates
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 53:12-25. 2012
  3. ncbi Abnormal circling behavior in rat mutants and its relevance to model specific brain dysfunctions
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Neurosci Biobehav Rev 34:31-49. 2010
  4. ncbi Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Seizure 20:359-68. 2011
  5. ncbi The pharmacokinetics of antiepileptic drugs in rats: consequences for maintaining effective drug levels during prolonged drug administration in rat models of epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Hannover, Germany
    Epilepsia 48:1245-58. 2007
  6. ncbi Drug transporters in the epileptic brain
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 48:8-13. 2007
  7. ncbi Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 47:1253-84. 2006
  8. ncbi mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent models of difficult-to-treat partial epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuropharmacology 50:1006-15. 2006
  9. ncbi Distribution of GABAergic neurons in the striatum of amygdala-kindled rats: an immunohistochemical and in situ hybridization study
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Brain Res 1083:50-60. 2006
  10. ncbi Mechanisms of drug resistance
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Epileptic Disord 7:S3-9. 2005

Research Grants

  1. Validation of rat models for resistant epilepsy therapy
    Wolfgang Loscher; Fiscal Year: 2005

Collaborators

Detail Information

Publications92

  1. ncbi Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Neuropharmacology 69:62-74. 2013
    ..This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'...
  2. ncbi How theories evolved concerning the mechanism of action of barbiturates
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 53:12-25. 2012
    ..Despite the remarkable progress of the last century, there is still much to learn about the actions of barbiturates that can be applied to the discovery of new, more therapeutically useful agents...
  3. ncbi Abnormal circling behavior in rat mutants and its relevance to model specific brain dysfunctions
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Neurosci Biobehav Rev 34:31-49. 2010
    ..The circling rat mutants described in this review illustrate how genetic animal models may serve to study multifaceted brain functions and dysfunctions, including disorders of the basal ganglia and vestibular system...
  4. ncbi Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Seizure 20:359-68. 2011
    ..To realize this goal, the molecular mechanisms of the next generation of therapies must necessarily evolve to include targets that contribute to epileptogenesis and pharmacoresistance in relevant epilepsy models...
  5. ncbi The pharmacokinetics of antiepileptic drugs in rats: consequences for maintaining effective drug levels during prolonged drug administration in rat models of epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Hannover, Germany
    Epilepsia 48:1245-58. 2007
    ....
  6. ncbi Drug transporters in the epileptic brain
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 48:8-13. 2007
    ..Cumulative clinical and experimental data support this hypothesis and offer novel therapeutic approaches for the treatment of drug-resistant epilepsy...
  7. ncbi Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 47:1253-84. 2006
    ..Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists...
  8. ncbi mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent models of difficult-to-treat partial epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuropharmacology 50:1006-15. 2006
    ..The present results do not support a significant anticonvulsant potential of group I mGlu receptor antagonists in rodent models of difficult-to-treat partial epilepsy...
  9. ncbi Distribution of GABAergic neurons in the striatum of amygdala-kindled rats: an immunohistochemical and in situ hybridization study
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Brain Res 1083:50-60. 2006
    ....
  10. ncbi Mechanisms of drug resistance
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Epileptic Disord 7:S3-9. 2005
    ....
  11. ncbi Drug resistance in brain diseases and the role of drug efflux transporters
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bunteweg 17, D 30559 Hannover, Germany
    Nat Rev Neurosci 6:591-602. 2005
    ..There is increasing evidence that drug efflux transporters have an important role in drug-resistant brain disorders, and this information should allow more efficacious treatment strategies to be developed...
  12. ncbi Cell and gene therapies in epilepsy--promising avenues or blind alleys?
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, 30559 Hannover, Germany
    Trends Neurosci 31:62-73. 2008
    ..However, several crucial issues remain to be resolved to develop cell and gene therapies into effective and safe therapies...
  13. ncbi Mechanisms of drug resistance in status epilepticus
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 48:74-7. 2007
    ..Improved understanding the molecular mechanisms underlying AED resistance in SE will ultimately provide new treatment options for RSE...
  14. ncbi Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary, Medicine, Hannover, Germany
    Curr Pharm Des 17:2808-28. 2011
    ..For translating these findings to the clinical arena, in vivo imaging studies using positron emission tomography (PET) with (11)C-labelled AEDs in epileptic patients are under way...
  15. ncbi Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 52:657-78. 2011
    ..In this respect, the authors of this critical review will discuss several new ideas that may hopefully lead to more efficacious drug treatment of epilepsy in the future...
  16. ncbi Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, Hannover, Germany
    Pharmacol Rev 62:668-700. 2010
    ..This article reviews these areas of progress and discusses the challenges associated with discovery of antiepileptogenic therapies...
  17. ncbi Functional, metabolic, and synaptic changes after seizures as potential targets for antiepileptic therapy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsy Behav 19:105-13. 2010
    ..As discussed in this review, enhanced understanding of these endogenous processes may lead to novel targets for AED development...
  18. ncbi Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Curr Top Med Chem 10:1785-91. 2010
    ....
  19. ncbi Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling
    Wolfgang Loscher
    Department of Pharmacology, University of Veterinary Medicine Hannover, Hannover D 30559, Germany
    Neurotherapeutics 6:258-62. 2009
    ....
  20. ncbi Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Eur J Pharmacol 610:1-11. 2009
    ..Furthermore, misconceptions regarding proconvulsant drug effects, which can result in the undertreatment of brain diseases, are discussed...
  21. ncbi The clinical impact of pharmacogenetics on the treatment of epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 50:1-23. 2009
    ..Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with epilepsy...
  22. ncbi Blood-brain barrier active efflux transporters: ATP-binding cassette gene family
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover D 30559, Germany
    NeuroRx 2:86-98. 2005
    ..Therefore, modulation of ABC efflux transporters at the BBB forms a novel strategy to enhance the penetration of drugs into the brain and may yield new therapeutic options for drug-resistant CNS diseases...
  23. ncbi New horizons in the development of antiepileptic drugs: the search for new targets
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany
    Epilepsy Res 60:77-159. 2004
    ..In this conference review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted...
  24. ncbi Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, 30559, Hannover, Germany
    Eur J Pharmacol 466:99-111. 2003
    ..In conclusion, it may be suggested that nicotinic acetylcholine receptor antagonism might be a valuable therapeutic approach to treat generalized epileptic seizures but rather not complex partial seizures...
  25. ncbi Critical re-evaluation of previous preclinical strategies for the discovery and the development of new antiepileptic drugs
    W Loscher
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, Hannover, Germany
    Epilepsy Res 50:17-20. 2002
    ..Overall, it was felt that the current preclinical strategies for the discovery and development of new AEDs have to be redefined in order to identify agents that are clearly superior to current medications...
  26. ncbi Multidrug resistance protein MRP2 contributes to blood-brain barrier function and restricts antiepileptic drug activity
    Heidrun Potschka
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    J Pharmacol Exp Ther 306:124-31. 2003
    ..In kindled MRP2-deficient rats, phenytoin exerted a markedly higher anticonvulsant activity than in normal rats. These data indicate that MRP2 substantially contributes to BBB function...
  27. ncbi New horizons in the development of antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, Hannover, Germany
    Epilepsy Res 50:3-16. 2002
    ..In this review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted...
  28. ncbi Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy
    Wolfgang Loscher
    Department of Pharmacology, School of Veterinary Medicine, Toxicology and Pharmacy, Hannover, Germany
    CNS Drugs 16:669-94. 2002
    ..In view of the advances in molecular neurobiology and neuroscience, future studies will undoubtedly further our understanding of the mechanisms of action of valproate...
  29. ncbi Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 45:1228-39. 2004
    ..Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP)...
  30. ncbi Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bunteweg 17, Hannover, Germany
    Epilepsy Res 50:105-23. 2002
    ....
  31. ncbi Role of multidrug transporters in pharmacoresistance to antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany
    J Pharmacol Exp Ther 301:7-14. 2002
    ..Furthermore, there are certainly other mechanisms of pharmacoresistance that need to be identified...
  32. ncbi Current status and future directions in the pharmacotherapy of epilepsy
    Wolfgang Loscher
    Dept of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, D 30551 Hannover, Germany
    Trends Pharmacol Sci 23:113-8. 2002
    ..In this article, I assess the current status of antiepileptic therapies and highlight innovative approaches for future treatments...
  33. ncbi Predictors of pharmacoresistant epilepsy: pharmacoresistant rats differ from pharmacoresponsive rats in behavioral and cognitive abnormalities associated with experimentally induced epilepsy
    Alexandra M Gastens
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Epilepsia 49:1759-76. 2008
    ..In the present study, we evaluated whether behavioral alterations in epileptic rats are different in AED nonresponders versus responders...
  34. ncbi Prophylactic treatment with levetiracetam after status epilepticus: lack of effect on epileptogenesis, neuronal damage, and behavioral alterations in rats
    Claudia Brandt
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuropharmacology 53:207-21. 2007
    ..These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats...
  35. ncbi Resistance to antiepileptic drugs and expression of P-glycoprotein in two rat models of status epilepticus
    Jens P Bankstahl
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsy Res 82:70-85. 2008
    ..The data suggest that, at least under the conditions of the present study, alterations in Pgp are not critically involved in refractory SE...
  36. ncbi High seizure frequency prior to antiepileptic treatment is a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsia 51:89-97. 2010
    ..In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals...
  37. ncbi Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and felbamate in ABCC2/MRP2-deficient TR- rats
    Heidrun Potschka
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsia 44:1479-86. 2003
    ..With brain microdialysis, we recently demonstrated that the AED phenytoin is subject to transport by ABCC2 at the BBB, whereas phenobarbital does not seem to be a substrate of ABCC2...
  38. ncbi Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice
    Christine J Müller
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Exp Neurol 219:284-97. 2009
    ..Our data indicate that the pilocarpine model of TLE in B6 mice is ideally suited to study the neurobiological mechanisms underlying the association between seizures, brain damage and psychopathology...
  39. ncbi Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy
    Claudia Brandt
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, D 30559 Hannover, Germany
    J Neurosci 30:8602-12. 2010
    ..These data do not indicate that bumetanide can prevent epilepsy after SE, but the disease-modifying effect of this drug warrants further studies with more lipophilic prodrugs of bumetanide...
  40. ncbi A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier
    Jens P Bankstahl
    Department of Pharmacology, University of Veterinary Medicine, and Center for Systems Neuroscience, 30559 Hannover, Germany
    J Neurosci 31:8803-11. 2011
    ..This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo...
  41. ncbi Animal models of drug-resistant epilepsy
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hanover, Germany
    Novartis Found Symp 243:149-59; discussion 159-66, 180-5. 2002
    ..We are currently studying the cellular mechanisms underlying the development of drug-resistant kindled seizures...
  42. ncbi Comparative analysis of anxiety-like behaviors and sensorimotor functions in two rat mutants, ci2 and ci3, with lateralized rotational behavior
    Sven Lindema
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Physiol Behav 93:417-26. 2008
    ..Based on previous findings of dysfunctions of the central dopamine system in ci2 and ci3 mutant rats, we assume that alterations in dopaminergic activity are involved in the maladaptive behavior observed in the present study...
  43. ncbi Antiepileptic drug resistant rats differ from drug responsive rats in GABA A receptor subunit expression in a model of temporal lobe epilepsy
    Kerstin Bethmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559, Hannover, Germany
    Neurobiol Dis 31:169-87. 2008
    ..Furthermore, upregulation of the alpha 4-subunit was observed in the CA1 of nonresponders. Our data suggest that alterations in GABA(A) receptor subtypes may be involved in resistance to AEDs...
  44. ncbi Resistance to phenobarbital extends to phenytoin in a rat model of temporal lobe epilepsy
    Kerstin Bethmann
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary, Medicine, Hannover, Germany
    Epilepsia 48:816-26. 2007
    ..Prolonged treatment of epileptic rats with phenobarbital (PB) resulted in two subgroups, PB responders and PB nonresponders...
  45. ncbi Benefits and risks of intranigral transplantation of GABA-producing cells subsequent to the establishment of kindling-induced seizures
    Marc W Nolte
    Department of Pharmacology, Neuroscience Discovery Research, Abbott GmbH and Co KG, Knollstrasse, 67061 Ludwigshafen, Germany
    Neurobiol Dis 31:342-54. 2008
    ..Thus, it appears that the condition of the host brain and the production of foreign proteins by transplanted cells have to be considered in estimating the risks of rejection of transplants into the brain...
  46. ncbi Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice
    Ina Gröticke
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Hannover, Germany
    Exp Neurol 207:329-49. 2007
    ..This makes these animals an ideal model to study the neurobiological mechanisms underlying the association between epilepsy and psychopathology...
  47. ncbi Subregional changes in discharge rate, pattern, and drug sensitivity of putative GABAergic nigral neurons in the kindling model of epilepsy
    Manuela Gernert
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Eur J Neurosci 20:2377-86. 2004
    ....
  48. ncbi Inter-individual variation in the anticonvulsant effect of phenobarbital in the pilocarpine rat model of temporal lobe epilepsy
    Marion Bankstahl
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany
    Exp Neurol 234:70-84. 2012
    ..These findings demonstrate that in the pilocarpine model, similar to epilepsy patients, epileptic rats differ in their response to an AED, which is most likely due to as yet unknown genetic factors...
  49. ncbi Therapeutic window of opportunity for the neuroprotective effect of valproate versus the competitive AMPA receptor antagonist NS1209 following status epilepticus in rats
    Melanie Langer
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Neuropharmacology 61:1033-47. 2011
    ..These data demonstrate that short treatment after SE with either VPA or NS1209 is powerfully neuroprotective, and may be disease-modifying treatments following brain insult...
  50. ncbi Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats
    Katrin Hoffmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 48:631-45. 2007
    ..This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats...
  51. ncbi Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport
    Konstantin Kuteykin-Teplyakov
    Department of Pharmacology, University of Veterinary Medicine, Hannover, Germany
    Br J Pharmacol 160:1453-63. 2010
    ..Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport...
  52. ncbi The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy
    Nadine Polascheck
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany
    Exp Neurol 224:219-33. 2010
    ..These results substantiate that COX-2 contributes to neuronal injury developing after SE, but inhibition of COX-2 is no effective means to modify epileptogenesis...
  53. ncbi Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein
    Steffen Baltes
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuropharmacology 52:333-46. 2007
    ....
  54. ncbi Retarded kindling progression in mice deficient in the extracellular matrix glycoprotein tenascin-R
    Katrin Hoffmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 50:859-69. 2009
    ....
  55. ncbi Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats
    Heidrun Potschka
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuroreport 15:1657-61. 2004
    ..The data indicate that P-glycoprotein expression levels in the kindled focus have a critical impact on the anticonvulsant response to antiepileptic drugs...
  56. ncbi Striking differences in proconvulsant-induced alterations of seizure threshold in two rat models
    Marion Bankstahl
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Neurotoxicology 33:127-37. 2012
    ....
  57. ncbi Impact of seizure activity on free extracellular phenytoin concentrations in amygdala-kindled rats
    Heidrun Potschka
    Institute of Pharmacology, Toxicology and Pharmacy, Ludwig Maximilians University, Munich, Germany
    Neuropharmacology 61:909-17. 2011
    ....
  58. ncbi Comparative analysis of anxiety-like behaviors and sensorimotor functions in two rat mutants, ci2 and ci3, with lateralized rotational behavior
    Sven Lindemann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Physiol Behav 91:551-60. 2007
    ..Based on previous findings of dysfunctions of the central dopamine system in ci2 and ci3 mutant rats, we assume that alterations in dopaminergic activity are involved in the maladaptive behavior observed in the present study...
  59. ncbi Complex time-dependent alterations in the brain expression of different drug efflux transporter genes after status epilepticus
    Konstantin Kuteykin-Teplyakov
    Department of Pharmacology, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Hannover, Germany
    Epilepsia 50:887-97. 2009
    ..However, the time course of alterations in Pgp or MRPs after seizures or SE is only incompletely known...
  60. ncbi Expression of the multidrug transporter MRP2 in the blood-brain barrier after pilocarpine-induced seizures in rats
    Katrin Hoffmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsy Res 69:1-14. 2006
    ....
  61. ncbi Genetically engineered GABA-producing cells demonstrate anticonvulsant effects and long-term transgene expression when transplanted into the central piriform cortex of rats
    Manuela Gernert
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine Hannover, , Hannover, Germany
    Exp Neurol 176:183-92. 2002
    ..The data demonstrate that genetically engineered cells have the potential to raise seizure thresholds when transplanted to the central PC...
  62. ncbi Striking differences in individual anticonvulsant response to phenobarbital in rats with spontaneous seizures after status epilepticus
    Claudia Brandt
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany
    Epilepsia 45:1488-97. 2004
    ....
  63. ncbi Marked strain and substrain differences in induction of status epilepticus and subsequent development of neurodegeneration, epilepsy, and behavioral alterations in rats. [corrected]
    Melanie Langer
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsy Res 96:207-24. 2011
    ....
  64. ncbi Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy
    Carlos Luna-Tortós
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neuropharmacology 58:1019-32. 2010
    ..The data indicate that common AEDs are not substrates for human MRP1, MRP2 or MRP5, at least in the in vitro models used in this study...
  65. ncbi Exposure to antiepileptic drugs does not alter the functionality of P-glycoprotein in brain capillary endothelial and kidney cell lines
    Kamila Ambroziak
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany
    Eur J Pharmacol 628:57-66. 2010
    ....
  66. ncbi The multidrug transporter hypothesis of drug resistance in epilepsy: Proof-of-principle in a rat model of temporal lobe epilepsy
    Claudia Brandt
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Neurobiol Dis 24:202-11. 2006
    ..These data demonstrate that inhibiting P-gp in epileptic rats with proven drug resistance counteracts resistance, providing the first proof-of-principle of the multidrug transporter hypothesis of medically refractory epilepsy...
  67. ncbi Valproic acid is not a substrate for P-glycoprotein or multidrug resistance proteins 1 and 2 in a number of in vitro and in vivo transport assays
    Steffen Baltes
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    J Pharmacol Exp Ther 320:331-43. 2007
    ..Thus, the molecular identity of the putative transporter(s) mediating the active efflux of VPA from the brain remains to be elucidated...
  68. ncbi Behavioral alterations in a mouse model of temporal lobe epilepsy induced by intrahippocampal injection of kainate
    Ina Gröticke
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Exp Neurol 213:71-83. 2008
    ..Our data suggest that the focal kainate model of mesial temporal lobe epilepsy may contribute to understanding the neurobiological mechanisms underlying the association between epilepsy and behavioral or cognitive alterations...
  69. ncbi Epileptic seizures and hippocampal damage after cuprizone-induced demyelination in C57BL/6 mice
    Katrin Hoffmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Exp Neurol 210:308-21. 2008
    ..The present data suggest a potential role of the hippocampal formation for seizures occurring as a consequence of neuronal damage secondary to CNS demyelination...
  70. ncbi 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
    Kathrin Töllner
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, 30559 Hannover, Germany
    J Neurosci 31:16423-34. 2011
    ..The data demonstrate for the first time an involvement of the SNr in pharmacoresistant experimental epilepsy and emphasize the relevance of the basal ganglia as target structures for new treatment options...
  71. ncbi Several major antiepileptic drugs are substrates for human P-glycoprotein
    Carlos Luna-Tortós
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany Center for Systems Neuroscience, Hannover, Germany
    Neuropharmacology 55:1364-75. 2008
    ..The present study provides the first direct evidence that several AEDS are substrates of human Pgp, thus further substantiating the transporter hypothesis of pharmacoresistant epilepsy...
  72. ncbi P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats
    Heidrun Potschka
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D 30559, Hannover, Germany
    Neurosci Lett 327:173-6. 2002
    ....
  73. ncbi Auditory and vestibular defects and behavioral alterations after neonatal administration of streptomycin to Lewis rats: Similarities and differences to the circling (ci2/ci2) Lewis rat mutant
    Marko Schirmer
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, Hannover, Germany
    Brain Res 1155:179-95. 2007
    ....
  74. ncbi Marked differences in response to dopamine receptor antagonism in two rat mutants, ci2 and ci3, with lateralized rotational behavior
    Marko Schirmer
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Hannover, Germany
    Behav Brain Res 180:218-25. 2007
    ..The comparative evaluation of these two rat mutants may help to increase our understanding of the relationship between developmental anomalies of cerebral asymmetry and brain disorders...
  75. ncbi Treatment with valproate after status epilepticus: effect on neuronal damage, epileptogenesis, and behavioral alterations in rats
    Claudia Brandt
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, , D-30559 Hannover, Germany
    Neuropharmacology 51:789-804. 2006
    ....
  76. ncbi Expression of the multidrug transporter P-glycoprotein in brain capillary endothelial cells and brain parenchyma of amygdala-kindled rats
    Ulrike Seegers
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hanover, Germany
    Epilepsia 43:675-84. 2002
    ..Furthermore, other multidrug transporters, such as multidrug resistance-associated protein, might be involved in the resistance of kindled rats to AEDs...
  77. ncbi Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and GABA(A) receptor ligand binding in a model of temporal lobe epilepsy
    Holger A Volk
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Neurobiol Dis 21:633-46. 2006
    ..The present data indicate that neurodegeneration and associated GABA(A) receptor changes in the dentate gyrus are critically involved in the mechanisms underlying refractoriness of seizures in TLE...
  78. ncbi Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats
    Claudia Brandt
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Epilepsia 47:1803-9. 2006
    ..Whether this indicates that lacosamide possesses antiepileptogenic or disease-modifying potential needs to be further evaluated, including studies in other models of acquired epilepsy...
  79. ncbi A comparison of extracellular levels of phenytoin in amygdala and hippocampus of kindled and non-kindled rats
    Heidrun Potschka
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany
    Neuroreport 13:167-71. 2002
    ....
  80. ncbi Transient increase of P-glycoprotein expression in endothelium and parenchyma of limbic brain regions in the kainate model of temporal lobe epilepsy
    Ulrike Seegers
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, , Building 218, D-30559 Hannover, Germany
    Epilepsy Res 51:257-68. 2002
    ..Seizure-induced over-expression of PGP in capillary endothelial cells of the BBB is likely to reduce the penetration of AEDs into brain parenchyma, which could explain the drug-refractoriness of seizures in TLE...
  81. ncbi Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET
    Jens P Bankstahl
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    J Nucl Med 49:1328-35. 2008
    ..To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB...
  82. ncbi Increased expression of the multidrug transporter P-glycoprotein in limbic brain regions after amygdala-kindled seizures in rats
    Holger A Volk
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, , Hannover D-30559, Germany
    Epilepsy Res 58:67-79. 2004
    ....
  83. ncbi Pedunculopontine neurons are involved in network changes in the kindling model of temporal lobe epilepsy
    Marc W Nolte
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, , 30559 Hannover, Germany
    Neurobiol Dis 23:206-18. 2006
    ..The underlying mechanisms are discussed. The findings are relevant for a better understanding of kindling-associated network changes and might provide new targets for therapeutic manipulations in epilepsies...
  84. ncbi Polymorphic variants of the multidrug resistance gene Mdr1a and response to antiepileptic drug treatment in the kindling model of epilepsy
    Cordula Baars
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Eur J Pharmacol 550:54-61. 2006
    ....
  85. ncbi Pilocarpine vs. lithium-pilocarpine for induction of status epilepticus in mice: development of spontaneous seizures, behavioral alterations and neuronal damage
    Christine J Müller
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Eur J Pharmacol 619:15-24. 2009
    ....
  86. ncbi Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia
    Angelika Richter
    Institute of Pharmacology and Toxicology, School of Veterinary Medicine, FU Berlin, Koserstrasse 20, 14195 Berlin, Germany
    Eur J Pharmacol 454:145-51. 2002
    ..In view of previous pathophysiological findings in mutant hamsters, the antidystonic efficacy of WIN 55,212-2 can be explained by modulation of different neurotransmitter systems within the basal ganglia...
  87. ncbi Delayed sclerosis, neuroprotection, and limbic epileptogenesis after status epilepticus in the rat
    Ulrich Ebert
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsia 43:86-95. 2002
    ..e., the development of recurrent spontaneous seizures) during the following weeks...
  88. ncbi Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats
    Claudia Brandt
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, , D-30559, Hannover, Germany
    Epilepsy Res 55:83-103. 2003
    ..The rat model provides a new tool to mimic different types of SE and investigate the pathogenesis underlying their long-term complications...
  89. ncbi Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures
    Holger A Volk
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
    Brain 128:1358-68. 2005
    ....
  90. ncbi The antiepileptic drug topiramate is a substrate for human P-glycoprotein but not multidrug resistance proteins
    Carlos Luna-Tortós
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
    Pharm Res 26:2464-70. 2009
    ..In this respect, it is important to know which AEDs are substrates for such drug transporters in humans...
  91. ncbi Increase in antiepileptic efficacy during prolonged treatment with valproic acid: role of inhibition of histone deacetylases?
    Katrin Hoffmann
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bunteweg 17, D 30559 Hannover, Germany
    Epilepsy Res 81:107-13. 2008
    ....
  92. ncbi Exposure of Fischer 344 rats to a weak power frequency magnetic field facilitates mammary tumorigenesis in the DMBA model of breast cancer
    Maren Fedrowitz
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    Carcinogenesis 29:186-93. 2008
    ..These data indicate that Fischer 344 rats are a suitable inbred strain to study the mechanisms underlying the effects of MF exposure on mammary tumorigenesis...

Research Grants1

  1. Validation of rat models for resistant epilepsy therapy
    Wolfgang Loscher; Fiscal Year: 2005
    ..Our goal is to establish standard assays that can be employed by researchers to continue the search for treatments of drug resistant epilepsy. ..