Posttraumatic secondary brain insults exacerbates neuronal injury by altering Metabotropic Glutamate Receptors

Abstract

Abstract Background Our previous studies indicated that metabotropic glutamate receptors (mGluRs) are deeply involved in the secondary processes after diffuse brain injury (DBI). In the present study, we used a rodent DBI model to determine whether hypotension exacerbates neuronal injury as a secondary brain insult (SBI) after traumatic brain injury (TBI) by changing the expression of metabotropic glutamate receptors (mGluRs) in the cerebral cortex. Results Three hundred and eleven male Sprague-Dawley rats were randomly assigned into five groups: normal control, sham-operated control, SBI alone, DBI alone, or DBI with SBI. DBI was produced in rats by Marmarou's methods and the SBI model was produced by hypotension. The alteration of neuronal expression of mGluRs after DBI and DBI coupled with SBI was observed by hybridization in situ at different time points in the experiment. We found a higher mortality and neurological severity score (NSS) for rats in the DBI with SBI group compared with those in the DBI alone group. Although there was a significant rise in the expression of group I and group III mGluRs (except mGluR6) and a decrease in the expression of group II mGluRs after DBI (P < 0.05), the changes were more severe when DBI was coupled with SBI (P < 0.05). The expression of group I mGluRs peaked at 24 hours, while the expression of the group III mGluRs peaked at 6 hours after injuries, which may reflect a self-protection first mechanism of the damaged neurons. Moreover, the overall neuro-harmful effects of mGluRs on neurons were seemly associated with higher mortality and NSS in the DBI with SBI group. Conclusion The results suggest posttraumatic SBI may exacerbate neuronal injury or brain injury by altering expression of mGluRs, and more emphasis should therefore be put on the prevention and treatment of SBI.