ERK1/2 activation in reactive astrocytes of mice with pilocarpine-induced status epilepticus

Objective: To investigate the activation pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) in the hippocampus of mice during pilocarpine-induced status epilepticus (SE) and its relationship with reactive astrogliosis. Methods: Status epilepticus (SE) models were established by intraperitoneal injection of pilocarpine. The intervention group received the ERK1/2 signaling pathway inhibitor SL327 before the pilocarpine injection. We evaluated the SE model group, the intervention group and the control saline-treated group, at 6 hours and 3 days after initiation of the seizure. Phosphorylated activated ERK1/2 and glial fibrillary acidic protein (GFAP) were labeled with both single-labeling and sequential single-labeling immunohistochemical techniques. Results: Among the pilocarpine-treated (SE model) mice, strong immunohistochemical staining of phospho-ERK1/2 was observed in the neurons and astrocytes of the hippocampus at 6 hours after initiation of SE, whereas staining on the third day of SE was not different from the control saline-treated mice. In the SL327-treated mice (intervention group), SL327 effectively blocked the ERK1/2 activation and little gliosis could be detected at 6 hours and 3 days after initiation of SE; the levels of phospho-ERK1/2 remained low, but the level of gliosis was similar to that of SE mice. Conclusion: The ERK1/2 signaling pathway plays an important role in the early stage of reactive astrogliosis in mice with pilocarpine-induced SE. [Neurol Res 2009; 31: 1108-1114]