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The Neuroprotective Effects of Non-NMDA Antagonists in the Cerebellum of the spastic Han Wistar Mutant

Authors
  • Nisim, A.A.
  • Hernandez, C.M.
  • Cohen, R.W.
Type
Published Article
Journal
Developmental Neuroscience
Publisher
S. Karger AG
Publication Date
Mar 12, 1999
Volume
21
Issue
1
Pages
76–86
Identifiers
DOI: 10.1159/000017369
PMID: 10077705
Source
Karger
Keywords
License
Green
External links

Abstract

Excitotoxicity resulting from the dysfunction of glutamate receptors has been attributed to neurodegeneration seen in many brain disorders. In our laboratory, the spastic Han Wistar mutant is currently utilized as a potential model of excitotoxicity. The mutant is characterized by progressive neuronal degeneration, hindlimb paresis and ataxia which culminates in the animal’s death at approximately 65 days of age. In this study, neuroprotection derived from acute administration of the non-NMDA antagonist GYKI 52466, and chronic administration of the non-NMDA antagonist CNQX was examined in order to determine the potential roles of non-NMDA receptors in the observed neurodegeneration. Mutants injected with GYKI 52466 (15 mg/kg), twice a week for 3 weeks, exhibited increased life spans (14%) and extended motor activity than their vehicle-treated mutant siblings. In a separate group of mutants, CNQX (either 50 or 500 μM) was infused directly into the third ventricle of the mutant’s brain utilizing osmotic pumps. A statistically significant increase in motor activity (22%) was detected for mutants treated with a dose of 50 μM CNQX compared to their vehicle-treated siblings. Finally, cerebellar histological evaluations of mutants treated with both 50 and 500 μM CNQX showed dose-dependent higher cerebellar Purkinje cell counts. These findings suggest that non-NMDA receptors play a significant role in neurodegeneration in this animal.

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