Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.

Abstract

Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection in multiple central nervous system injury, but the roles of mGluR5 in subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG or positive allosteric modulator VU0360172 administration significantly improves neurological function and attenuates brain edema at 24 h after SAH. Furthermore, mGluR5 obviously expresses in activated microglia (ED-1 positive) after SAH. CHPG or VU0360172 administration significantly reduces the numbers of activated microglia and the protein and mRNA levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α at 24 h after SAH. Moreover, CHPG or VU0360172 administration obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN-positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration significantly up-regulates the expression of Bcl-2, and down-regulates the expression of Bax and active caspase-3, which in turn increases the ratio of Bcl-2/Bax. Our results indicate that activation of mGluR5 attenuates microglial activation and neuronal apoptosis, and improves neurological function in EBI after SAH.