Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study

Brief periods of global cerebral ischemia are known to produce characteristic patterns of neuronal injury both in human studies and in experimental animal models. Ischemic damage to vulnerable areas such as the CA1 sector of the hippocampus is thought to result from excitotoxic amino acid neurotrans...

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Bibliographic Details
Published in:Brain research 1997-10, Vol.770 (1), p.115-122
Main Authors: Owen, Andrew J, Ijaz, Sadiq, Miyashita, Hiro, Wishart, Tom, Howlett, Wendy, Shuaib, Ashfaq
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - pharmacology
Behavior
Behavior, Animal - physiology
Disease Models, Animal
Gerbil
Gerbillinae
Global ischemia
Glutamate
Glutamic Acid - metabolism
Hippocampus
Hippocampus - blood supply
Hippocampus - pathology
Hippocampus - physiopathology
Histology
Ischemic Attack, Transient - drug therapy
Isoxazoles - pharmacology
Male
Maze Learning - physiology
Microdialysis
Neuroprotection
Neuroprotective Agents - pharmacology
Prosencephalon - blood supply
Prosencephalon - pathology
Prosencephalon - physiopathology
Silver Staining
Zonisamide
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Summary:Brief periods of global cerebral ischemia are known to produce characteristic patterns of neuronal injury both in human studies and in experimental animal models. Ischemic damage to vulnerable areas such as the CA1 sector of the hippocampus is thought to result from excitotoxic amino acid neurotransmission. The objective of this study was to determine the ability of a novel sodium channel blocking compound, zonisamide, to reduce neuronal damage by preventing the ischemia-associated accumulation of extracellular glutamate. Using a gerbil model, animals were subjected to 5 min ischemic insults. Both pre- and post-ischemic drug administration (zonisamide 150 mg/kg) were studied. Histological brain sections were prepared using a silver stain at 7 and 28 days post ischemia. The animals sacrificed at 28 days also underwent behavioral testing using a modified Morris water maze. In vivo microdialysis was performed on a separate group of animals in order to determine the patterns of ischemia-induced glutamate accumulation in the CA1 sector of the hippocampus. Pyramidal cell damage scores in the CA1 region of the hippocampus were significantly reduced in animals pre-treated with zonisamide compared to saline-treated controls, both at 7 days (drug pre-treated: 0.812±0.28, n=8; controls: 1.625±0.24, n=8; * P
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(97)00789-0