The effect of groups II and III metabotropic glutamate receptor activationon neuronal injury in a rodent model of traumatic brain injury

OBJECTIVE: The role of metabotropic glutamate receptor activation after tra umatic brain injury (TBI) is not well understood. In vitro studies suggest that activation of Groups II and III metabotropic glutamate receptors may p rovide some degree of neuroprotection and may be potential targets for the development of therapeutic strategies. Thus, we examined the effects of Gro up II and Group III selective agonists on neuronal degeneration after in vi vo TBI. METHODS: fifty male Sprague-Dawley rats were subjected to lateral fluid per cussion brain injury immediately followed by an intracranial injection of 2 -(2',3')-dicarboxycyclopropylglycine (DCG-IV) (Group II) or (R,S)-4-phospho nophenylglycine (Group III) in the CA2 and CA3 areas of the hippocampus. DC G-IV was injected at doses of 20 fmol, 100 fmol, and 500 fmol, and (R,S)-4- phosphonophenylglycine was injected at 8 nmol, 40 nmol, and 200 nmol. Vehic le injection control groups were used for comparison with each drug group. All animals were killed 24 hours after TBI was induced. Four 50-mum brain s ections were obtained from each animal and stained for degenerating neurons with the fluorochrome Fluoro-Jade. Two independent, blinded investigators counted the number of degenerating (Fluoro-Jade-positive) neurons in the CA 2 and CA3 areas of the hippocampus of each brain section. RESULTS: Compared with vehicle, the 500-fmol dose of DCG-IV significantly r educed the number of Fluoro-Jade-positive degenerating neurons (P < 0.001). Lower doses of DCG-IV were associated with a decreased but not statistical ly significant number of Fluoro-Jade-positive neurons. In contrast, (R,S)-4 -phosphonophenylglycine had no significant effect on the number of degenera ting neurons. CONCLUSION: Administration of selective Group II metabotropic glutamate rec eptor agonists protects neurons against in vive TBI. These receptors may th us be a promising target for future neuroprotective drugs.