Effect Of Phosphorylation Of P38 Mitogen-Activated Protein Kinase On Homer1a Expression In The Cortex Of Rats With Diffuse Brain Injury

Objective: To investigate the effect of p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 on phosphorylated p38 MAPK and Homer1a in the cortex of rats with diffuse brain injury (DBI). Method: Rat DBI model was established using Marmarou's method in the central laboratory in the Department of Neurosurgery of North China university of Science and Technology. 149 male Sprague-Dawlley rats were divided into sham operation (SO) group, DBI group and DBI+ SB203580 intervention group (intraperitoneal injection, 0.01 mu g/kg). Brain tissues were removed from each group at 1 h, 6 h, 24 h, 48 h, and 72 h after injury, respectively. Cerebral cortex neutrons were observed under the optic microscope and electron microscope for morphological changes. Levels of phosphorylated p38 MARPK and Homer1a were detected using immunohistochemistry and immunoblotting. Statistical analysis of experimental data was conducted using SPSS 17.0. Intergroup factorial ANOVA was conducted. P < 0.05 indicated that differences were statistically different. Results: Compared with SO group, degeneratie and necrotic changes were observed in some cerebral cortex neurons of DBI group rats and the number of alived neurons was reduced. Phosphorylated p38 MAPK level was elevated at each time point, reaching a peak level at 24 h and decreasing at 48 h and 72 h (0.694 +/- 0.26 vs. 0.224 +/- 0.07; 0.982 +/- 0.38 vs. 0.220 +/- 0.09; 1.146 +/- 0.66 vs. 0.224 +/- 0.08; 0.864 +/- 0.32 vs. 0.220 +/- 0.09; 0.680 +/- 0.28 vs. 0.218 +/- 0.08; all P < 0.05). Homer 1a expression level was elevated at each time point, reaching a peak level at 24 h and decreasing at 48 h and 72 h, but still higher than that of SO group (0.096 +/- 0.020 vs. 0.011 +/- 0.010; 0.144 +/- 0.026 vs. 0.010 +/- 0.009; 0.172 +/- 0.030 vs. 0.010 +/- 0.010; 0.136 +/- 0.023 vs. 0.010 +/- 0.010; 0.114 +/- 0.020 vs. 0.011 +/- 0.019; all P < 0.05). Compared with DBI group, DBI+ SB203580 group exhibited reduced morphological and structural lesions in cerebral tissues, increased number of alive neurons, significant decrease of phosphorylated p38 MAPK level at each time point (0.380 +/- 0.18 vs. 0.694 +/- 0.26; 0.556 +/- 0.29 vs. 0.982 +/- 0.38; 0.698 +/- 0.36 vs. 1.146 +/- 0.66; 0.542 +/- 0.28 vs. 0.864 +/- 0.32, 0.378 +/- 0.26 vs. 0.680 +/- 0.28, all P < 0.05), and significantly enhanced expression level of Homer1a at each time point 0.156 +/- 0.026 vs. 0.096 +/- 0.020; 0.198 +/- 0.029 vs. 0.144 +/- 0.026; 0.246 +/- 0.038 vs. 0.172 +/- 0.030; 0.154 +/- 0.021 vs. 0.136 +/- 0.023, 0.132 +/- 0.012 vs. 0.114 +/- 0.020, all P < 0.05). Conclusion: The post DBI expression level of Homer1a in the cortex was associated with p38 MAPK activation. Inhibition of p38 MAPK phosphorylation elevated expression of Homer1a and reduced apoptosis of neurons in the cortex.