Brittain, Joel M.Chen, LiangWilson, Sarah M.Brustovetsky, TatianaGao, XiangAshpole, Nicole M.Molosh, Andrei I.You, HaitaoHudmon, AndyShekhar, Anantha S.White, Fletcher A.Zamponi, Gerald W.Brustovetsky, Nickolay N.Chen, JinhuiKhanna, Rajesh2018-06-062018-06-062011-08-09Brittain, J. M., Chen, L., Wilson, S. M., Brustovetsky, T., Gao, X., Ashpole, N. M., … Khanna, R. (2011). Neuroprotection against traumatic brain Injury by a peptide derived from the Collapsin Response Mediator Protein 2 (CRMP2). Journal of Biological Chemistry, 286(43), 37778–37792. https://doi.org/10.1074/jbc.M111.255455http://hdl.handle.net/1880/106723https://doi.org/10.11575/PRISM/43823Neurological disabilities following traumatic brain injury (TBI) may be due to excitotoxic neuronal loss. The excitotoxic loss of neurons following TBI occurs largely due to hyperactivation of N-methyl-d-aspartate receptors (NMDARs), leading to toxic levels of intracellular Ca(2+). The axon guidance and outgrowth protein collapsin response mediator protein 2 (CRMP2) has been linked to NMDAR trafficking and may be involved in neuronal survival following excitotoxicity. Lentivirus-mediated CRMP2 knockdown or treatment with a CRMP2 peptide fused to HIV TAT protein (TAT-CBD3) blocked neuronal death following glutamate exposure probably via blunting toxicity from delayed calcium deregulation. Application of TAT-CBD3 attenuated postsynaptic NMDAR-mediated currents in cortical slices. In exploring modulation of NMDARs by TAT-CBD3, we found that TAT-CBD3 induced NR2B internalization in dendritic spines without altering somal NR2B surface expression. Furthermore, TAT-CBD3 reduced NMDA-mediated Ca(2+) influx and currents in cultured neurons. Systemic administration of TAT-CBD3 following a controlled cortical impact model of TBI decreased hippocampal neuronal death. These findings support TAT-CBD3 as a novel neuroprotective agent that may increase neuronal survival following injury by reducing surface expression of dendritic NR2B receptors.enjournal articlehttp://dx.doi.org/10.1074/jbc.M111.255455