No improvement of functional and histological outcome after application of the metabotropic glutamate receptor 5 agonist CHPG in a model of endothelin-1-induced focal ischemia in rats

The role of group I metabotropic glutamate receptors (mGluRs) in neurodegeneration is as yet unclear as mGluR1/5 antagonists and agonists yielded contradictory effects in different disease models. In the present study, we examined the neuroprotective potency of the selective mGluR5 agonist, (R,S)-2-...

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Bibliographic Details
Published in:Neuroscience research 2007-04, Vol.57 (4), p.499-503
Main Authors: Riek-Burchardt, M., Henrich-Noack, P., Reymann, K.G.
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
Brain Infarction - drug therapy
Brain Infarction - etiology
CHPG
Disease Models, Animal
Endothelin-1
Excitatory Amino Acid Agonists - therapeutic use
Focal ischemia
Functional outcome
Glycine - analogs & derivatives
Glycine - therapeutic use
Ischemia - chemically induced
Ischemia - drug therapy
Ischemia - pathology
Ischemia - physiopathology
Late time point
Male
Phenylacetates - therapeutic use
Psychomotor Performance - drug effects
Rats
Rats, Sprague-Dawley
Time Factors
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Summary:The role of group I metabotropic glutamate receptors (mGluRs) in neurodegeneration is as yet unclear as mGluR1/5 antagonists and agonists yielded contradictory effects in different disease models. In the present study, we examined the neuroprotective potency of the selective mGluR5 agonist, (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), in endothelin-1(ET-1)-induced focal ischemia in rats. In addition to the effect of CHPG on the histologically defined infarct size, we studied its influence on sensorimotor impairments in the ladder rung walking test at late time points up to 4 weeks after the ischemic insult. Rats were treated i.c.v. with an injection of 1 mM CHPG beginning 10 min after the application of ET-1. Histological analyses 4 weeks after ET-1-induced ischemia demonstrated only a small, insignificant reduction in infarct size after CHPG application. In accordance with this result, there were no significant effects of the used CHPG concentration on sensorimotor impairments in the ladder rung walking test. In conclusion, our data point to the restricted value of CHPG as a neuroprotectant after transient focal ischemia and to the importance of evaluating neuroprotective effects at late post-ischemic time points.
ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2006.12.006