Document Detail

Predictors of pharmacoresistant epilepsy: pharmacoresistant rats differ from pharmacoresponsive rats in behavioral and cognitive abnormalities associated with experimentally induced epilepsy.
MedLine Citation:
PMID:  18494789     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Patients with intractable temporal lobe epilepsy (TLE) exhibit an increased risk of psychiatric comorbidity, including depression, anxiety, psychosis, and learning disorders. Furthermore, a history of psychiatric comorbidity has been suggested as a predictor of lack of response to therapy with antiepileptic drugs (AEDs) in patients with epilepsy. However, clinical studies on predictors of pharmacoresistant epilepsy are affected by several confounding variables, which may complicate conclusions. In the present study, we evaluated whether behavioral alterations in epileptic rats are different in AED nonresponders versus responders. METHODS: For this purpose, we used an animal model of TLE in which AED responders and nonresponders can be selected by prolonged treatment of epileptic rats with phenobarbital (PB). Behavioral and cognitive abnormalities were compared between responders and nonresponders as well as between epileptic rats and nonepileptic controls in a battery of tests. RESULTS: Fifteen epileptic rats with spontaneous recurrent seizures (SRS) either responding (11 rats) or not responding (4 rats) to PB were used for this study. The nonresponders differed markedly in behavioral and cognitive abnormalities from responders and nonepileptic controls in tests of anxiety (open field, elevated-plus maze test), behavioral hyperexcitability (approach-response, touch-response, pick-up tests), and learning and memory (Morris water maze). DISCUSSION: Our hypothesis that AED-resistant rats will show more severe behavioral and cognitive changes than AED-responsive rats was confirmed by the present experiments. The data substantiate that rodent models of TLE are useful to delineate predictors of pharmacoresistant epilepsy.
Alexandra M Gastens; Claudia Brandt; Jens P Bankstahl; Wolfgang Löscher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-20
Journal Detail:
Title:  Epilepsia     Volume:  49     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-31     Completed Date:  2008-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1759-76     Citation Subset:  IM    
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.
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MeSH Terms
Amygdala / physiology,  radiation effects
Analysis of Variance
Anticonvulsants / therapeutic use*
Behavior, Animal / drug effects*
Cognition Disorders / drug therapy*,  etiology*
Disease Models, Animal
Drug Resistance* / drug effects
Electric Stimulation / adverse effects
Electroencephalography / methods
Epilepsy / complications*,  etiology,  pathology,  prevention & control
Exploratory Behavior / drug effects
Hippocampus / pathology
Maze Learning / drug effects
Phenobarbital / therapeutic use
Predictive Value of Tests
Rats, Sprague-Dawley
Recurrence / prevention & control
Statistics, Nonparametric
Swimming / physiology
Time Factors
Grant Support
Reg. No./Substance:
0/Anticonvulsants; 50-06-6/Phenobarbital

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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