Activation of Metabotropic Glutamate Receptor Subtype mGluR1 Contributes to Post-Traumatic Neuronal Injury

Abstract

The role of phospholipase C-coupled (group I) metabotropic glutamate receptors (mGluR1 and mGluR5) in post-traumatic neuronal injury was examined using ratin vivoandin vitromodels. Traumatic injury to mixed neuronal/glial cultures induced phosphoinositide hydrolysis and caused neuronal death. Pharmacological blockade of group I receptors significantly reduced these effectsin vitroand decreased neurological deficits as well as neuronal loss produced by traumatic brain injuryin vivo.In contrast, activation of group I receptors by a specific agonistin vitroexacerbated post-traumatic neuronal death in a dose-dependent manner. Antisense oligodeoxynucleotide directed to mGluR1, but not to mGluR5, was neuroprotectivein vitro, although each oligodeoxynucleotide reduced the respective receptor-stimulated accumulation of inositol phosphates to a similar degree. Together, these findings suggest that activation of mGluR1 contributes to post-traumatic neuronal injury and that mGluR1 antagonists may have therapeutic potential in brain injury.