Ischemic brain cell death is presumably caused by excitotoxicity. In addition to an increase of glutamate release during ischemia, the deficiency of astrocytic glutamate-reuptake may cause glutamate accumulation, which results in GABAergic neurons being vulnerable to ischemia. To confirm this hypothesis, we studied the pathophysiological changes of cortical astrocytes and GABAergic neurons during ischemia as well as the prevention of their injuries. Ischemia led to the sequential impairments of astrocytic glutamate-transporter currents and GABAergic neuronal excitability. The changes were partially reversed by 3,5-DHPG, an agonist of type-I/V metabotropic glutamate receptors (mGluR). Thus, mGluR₁,₅ activation may be useful against the sequential impairment of cortical astrocytes and GABAergic neurons in an early stage of ischemia.