The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway.

Abstract

Group I metabotropic glutamate receptors (mGluRs) have been implicated in the pathophysiology of central nervous system injury, but the role of mGluR5 in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the neuroprotective potency of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), a selective mGluR5 agonist, for protecting against TBI in both in vitro and in vivo models. Primary cortical neurons were treated with 1 mM CHPG in an in vitro preparation 30 min before TBI, and 250 nM CHPG was injected into the right lateral ventricle of rats 30 min before TBI was induced in in vivo studies. The results showed that CHPG significantly attenuated lactate dehydrogenase (LDH) release and neuronal apoptosis and reduced lesion volume. Compared to the control or vehicle group, the phosphorylation levels of extracellular signal-regulated kinase (ERK) and Akt were increased in the presence of CHPG, even following the induction of TBI. Furthermore, treatment with either the ERK inhibitor PD98059 or Akt inhibitor LY294002 partially reversed the CHPG's neuroprotective effects. These data suggest that CHPG minimizes brain damage after induction of TBI both in vitro and in vivo, and that these protective effects were possibly mediated by activation of the ERK and Akt signaling pathways. Thus, potentiating mGluR5 activity with selective agonists such as CHPG may be useful for the treatment of traumatic brain injury.

• Authors: Tao Chen, Lei Zhang, Yan Qu, Kai Huo, Xiaofan Jiang, Zhou Fei
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 29 Issue 4 Pg. 630-6 (Apr 2012) ISSN: 1791-244X [Electronic] Greece
• PMID: 22211238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-chloro-5-hydroxyphenylglycine
• Chromones
• Grm5 protein, rat
• Morpholines
• Neuroprotective Agents
• Phenylacetates
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• L-Lactate Dehydrogenase
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• Glycine

Topics

• Animals
• Brain Injuries (drug therapy, pathology)
• Cells, Cultured
• Chromones (metabolism)
• Glycine (analogs & derivatives, pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• Morpholines (metabolism)
• Neuroprotective Agents (pharmacology)
• Phenylacetates (pharmacology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate (agonists)
• Signal Transduction