The mGlu receptor ligand (S)-4C3HPG protects neurons after global ischaemia in gerbils

(S)-4-Carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG] is a potent competitive antagonist at the metabotropic glutamate receptor 1 subtype (mGlu1 receptor) and an agonist at mGlu2/3 receptor. We evaluated histologically the effect of this compound on transient global ischaemia in gerbils and observed pronounced neuroprotection in the CA1 layer of the hippocampus. When (S)-4C3HPG (1 microM) was administered intra-cerebroventricularly (i.c.v.) 20 min before clamping both common carotid arteries neuronal density was comparable with that in sham-operated animals. A single injection (1 microM) 65 min after ischaemia also significantly reduced neuronal damage. The results suggest that metabotropic glutamate receptors play a role in the deleterious cascade which leads to neuronal damage of pyramidal cells in the CA1 layer of the hippocampus after transient global ischaemia.