1‐Aminoindan‐1,5‐dicarboxylic acid and (S)‐(+)‐2‐(3′‐carboxybicyclo(1.1.1) pentyl)‐glycine, two mGlu1 receptor‐preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia

1‐Aminoindan‐1,5‐dicarboxylic acid and (S)‐(+)‐2‐(3′‐carboxybicyclo(1.1.1)... Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently‐characterized and relatively selective mGlu1 receptor antagonists 1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) and (S)‐(+)‐2‐(3′‐carboxybicyclo(1.1.1)pentyl)‐glycine (CBPG) could reduce neuronal death in vitro, following oxygen‐glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine ((+)MCPG) and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (–)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD) and the group I mGlu receptor agonist 3,5‐dihydroxyphenylglycine (3,5‐DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i.c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

1‐Aminoindan‐1,5‐dicarboxylic acid and (S)‐(+)‐2‐(3′‐carboxybicyclo(1.1.1) pentyl)‐glycine, two mGlu1 receptor‐preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia

Loading next page...
 
/lp/wiley/1-aminoindan-1-5-dicarboxylic-acid-and-s-2-3-carboxybicyclo-1-1-1-0ZKDJNdCxx
Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
D.O.I.
10.1046/j.1460-9568.1999.00786.x
Publisher site
See Article on Publisher Site

Abstract

Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently‐characterized and relatively selective mGlu1 receptor antagonists 1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) and (S)‐(+)‐2‐(3′‐carboxybicyclo(1.1.1)pentyl)‐glycine (CBPG) could reduce neuronal death in vitro, following oxygen‐glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine ((+)MCPG) and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (–)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD) and the group I mGlu receptor agonist 3,5‐dihydroxyphenylglycine (3,5‐DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i.c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection.

Journal

European Journal of NeuroscienceWiley

Published: Oct 1, 1999

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off