RESUMO
AIM: To investigate the effect of extracellular signal-regulated kinase 1/2 signaling pathway after severe diffuse brain injury (DBI) in rats, and to provide base for treatment. METHODS: Male Sprague-Dawley rats were randomly divided into four groups: control group, traumatic group, low dose of inhibitor U0126 treatment group and high dose of inhibitor U0126 treatment group. DBI rat model was established according to the description of Marmarou's diffused brain injury. At 30 min and 1 h, 6 h, 24 h, 48 h and 72 h after injury, morphological changes were observed under light and electronic microscopes. The ERK1/2 phosphorylation and c-Fos were measured by Western blotting. Apoptosis was measured with TUNEL method. Learning and memory function were performed with Morris water maze from 3 days to 7 days after injury. RESULTS: After trauma, some neurons displayed histopathologic changes of necrosis and apoptosis, axon myelin sheath internalization and disconnection. ERK1/2 phosphorylation protein was apparently increased at 30 min after injury, approached peak at 6 h and continued to 24 h. c-fos protein was markedly increased at 30 min after injury, approached peak at 6 h and returned to bottom at 24 h. The number of apoptotic nerve cells increased at 6 h after and approached peak at 72 h. Latencies of searching safety island prolonged. Rats treated with U0126 had reduction in ERK1/2 activity, c-Fos protein, neuronal apoptosis and searching safety island latencies. CONCLUSION: The activated ERK1/2 signaling pathway plays an important role in processing of nerve cell apoptosis after severe DBI.