Neuroprotective Effects of Selective Group II mGluR Activation in Brain Trauma and Traumatic Neuronal Injury

The effects of group II mGluR activation by selective agonist (–)-2-oxa-4-aminobicyclo[3.1. 0]hexane-4,6-dicarboxylate (LY379268) were examined in a mouse model of controlled cortical impact(CCI)–induced brain injury and in primary neuronal/glial and neuronal cultures subjected to mechanical trauma. Systemic administration of LY379268 to mice at 30 min after CCI significantly improved both motor and cognitive recovery as compared with vehicle-treated control animals. LY379268 also significantly reduced cell death induced by mechanical injury in rat neuronal/glial and neuronal cultures, as measured by lactate dehydrogenase (LDH) release assay. The neuroprotective effect of LY379268 in vitro was abolished by co-administration of the mGluR2/3 antagonist(s)-α-ethylglutamic acid (EGLU); however, co-application of selective mGluR3 antagonist β-Nacetyl- aspartyl-glutamate (NAAG) had no significant influence in the same system. Together, these findings demonstrate the neuroprotective activity of group II mGluR activation and underscore the role of the mGluR2 subtype for this effect.