mGluR1,5 activation protects cortical astrocytes and GABAergic neurons from ischemia-induced impairment

Ischemic neuron death is presumably caused by excitotoxicity. Here, we studied whether ischemia impaired astrocytes and GABAergic neurons to exacerbate glutamate-dependent neural excitotoxicity by electrophysiologically recording these nerve cells in cortical slices. Our results showed that ischemia impaired the activity of glutamate-transporters (Glu-T) on the astrocytes, as well as the ability of firing spikes and the response to excitatory synaptic inputs on GABAergic neurons. The impairments of glutamate reuptakes and GABAergic neurons led to the imbalance between excitation and inhibition toward neural excitotoxicity. When explored the protection of nerve cells from ischemia, we found that the ischemic impairments of astrocytes and GABAergic cells were prevented by 3,5-DHPG, an agonist for type-I/V of metabotropic glutamate receptors (mGluR). The activation of mGluR1,5 is likely a potential therapeutic strategy to prevent nervous tissues from excitotoxicity by reducing the impairment of the astrocytes and GABAergic neurons during the early stage of ischemia.

► Ischemia impairs the activity of glutamate-transporter at cortical astrocytes.
► Ischemia impairs action potential and synaptic transmission at GABAergic cells.
► mGluR1,5 activation reverses ischemic impairments of astrocytes and GABA cells.