Group II metabotropic glutamate receptor activation attenuates traumatic neuronal injury and improves neurological recovery after traumatic brain injury

We examined the effects of modulating group II metabotropic glutamate recep tors (mGluRs) on traumatic neuronal injury using both in vitro and in vivo models. Treatment with various selective group II mGluR agonists significan tly decreased lactate dehydrogenase release, a marker of cell death, after traumatic injury to rat neuronal-glial cultures; injury-induced increases i n cyclic AMP and glutamate levels were also significantly reduced by a grou p Il agonist. The neuroprotective effects of group II agonists were markedl y attenuated by co-administration of a group II antagonist or a membrane-pe rmeable cyclic AMP analog and were additive to those provided by an N-methy l-D-aspartate receptor antagonist or a selective group I mGluR antagonist. Administration of a group II mGluR agonist 30 min after lateral fluid percu ssion-induced brain injury in rats significantly improved subsequent behavi oral recovery as compared with vehicle-treated controls. Together these stu dies indicate that group II mGluR agonists protect against traumatic neuron al injury by attenuating glutamate release and cAMP levels and suggest a po tential role for these agents in the treatment of clinical neurotrauma.