The major findings of the present study are: i) The selective mGluR5 agonist CHPG attenuated neuronal damage after traumatic injury in vitro; ii) CHPG reduced neuronal apoptosis and lesion volume in an in vivo model of TBI; iii) CHPG enhanced the expression of p-ERK and p-Akt after traumatic brain injury; iv) Activated ERK and Akt both contribute to the protective effects of CHPG against TBI. The gene discussed is AKT1; the disease is brain injury.