Document Detail


Transmeningeal delivery of GABA to control neocortical seizures in rats.
MedLine Citation:
PMID:  17478079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transmeningeal drug delivery, using an implanted hybrid neuroprosthesis, has been proposed as a novel therapy for intractable focal epilepsy. As part of a systematic effort to identify the optimal compounds and protocols for such a therapy, this study aimed to determine whether transmeningeal gamma-aminobutyric acid (GABA) delivery can terminate and/or prevent neocortical seizures in rats. Rats were chronically implanted with an epidural cup and an adjacent EEG electrode in the right parietal cortex. While the rat was behaving freely, a seizure-inducing concentration of acetylcholine (Ach) was applied into the cup. In a seizure termination study, either artificial cerebrospinal fluid (ACSF) or GABA (0.25, 2.5, 25 or 50mM) was delivered into the exposed neocortical area during an ongoing seizure. In a seizure prevention study, either ACSF or 50mM GABA was delivered into the epidural cup before the application of Ach. Epidural delivery of 50mM GABA completely terminated ongoing Ach-induced EEG seizures and convulsions within 17-437s after its delivery. ACSF and lower concentrations of GABA did not produce this effect, but 25mM GABA reduced seizure severity. However, the used GABA concentration could not prevent the development, or affect the severity, of Ach-induced EEG seizures and convulsions. This study indicates that transmeningeal GABA delivery can be used for terminating neocortical seizures, but to achieve seizure prevention via this route either a more efficient GABA delivery method needs to be developed or other neurotransmitters/pharmaceuticals should be employed for this purpose.
Authors:
Jenine E John; Shirn L Baptiste; Lynette G Sheffield; Hans von Gizycki; Ruben I Kuzniecky; Orrin Devinsky; Nandor Ludvig
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Publication Detail:
Type:  Journal Article     Date:  2007-05-02
Journal Detail:
Title:  Epilepsy research     Volume:  75     ISSN:  0920-1211     ISO Abbreviation:  Epilepsy Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-08     Completed Date:  2007-08-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8703089     Medline TA:  Epilepsy Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  10-7     Citation Subset:  IM    
Affiliation:
Comprehensive Epilepsy Center, Department of Neurology, NYU School of Medicine, New York, NY 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine
Analysis of Variance
Animals
Anticonvulsants / administration & dosage*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Routes
Drug Interactions
Electroencephalography
Fourier Analysis
Glial Fibrillary Acidic Protein / metabolism
Male
Neocortex / drug effects*
Rats
Rats, Long-Evans
Seizures / chemically induced,  drug therapy*,  pathology,  physiopathology
gamma-Aminobutyric Acid / administration & dosage*
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Glial Fibrillary Acidic Protein; 51-84-3/Acetylcholine; 56-12-2/gamma-Aminobutyric Acid

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


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