Changes in metabotropic glutamate receptor 4 expression and the effects of L-2-amino-4-phosphonobutyrate in a rodent model of diffuse brain injury / 中华创伤杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To examine the changes in the expression of mGluR4 after diffuse brain injury (DBI) and to determine the role of its specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) in vivo.</p><p><b>METHODS</b>A total of 161 male SD rats were randomized into the following groups. Group A included normal control, sham-operated control and DBI group. DBI was produced according to Marmarou's diffuse head injury model. mRNA expression of mGluR4 was detected by hybridization in situ. Group B included DBI alone, DBI treated with normal saline and DBI treated with L-AP4. All DBI rats were trained in a series of performance tests, following which they were subjected to DBI. At 1 and 12 hours, animals were injected intraventricularly with L-AP4 (100 mmol/L, 10 microl) or normal saline. Motor and cognitive performances were tested at 1, 3, 7, 14 days after injury and the damaged neurons were also detected.</p><p><b>RESULTS</b>There was no significant difference between normal control group and sham-operated group in the expression of mGluR4 (P>0.05). The animals exposed to DBI showed significantly increased expression of mRNA of mGluR4 compared with the sham-operated animals 1 h after injury (P<0.05). At 6 hours, the evolution of neuronal expression of mGluR4 in the trauma alone group was relatively static. Compared with saline-treated control animals, rats treated with L-AP4 showed an effective result of decreased number of damaged neurons and better motor and cognitive performances.</p><p><b>CONCLUSIONS</b>Increased expression of mGluR4 is important in the pathophysiological process of DBI and its specific agonist L-AP4 can provide remarkable neuroprotection against DBI not only at the histopathological level but also in the motor and cognitive performance.</p>