Characterization of osteopontin expression and function after status epilepticus

Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE. Methods: Pilocarpine was used to induce SE in OPN-/- and OPN+/+ mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochernistry. The effect of added osteopontin on excitotoxicity by N-methyl-D-aspartate in neuronal cultures of ONP-/- mice was determined. Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2-3 days after SE. After 10 to 31 days degenerating axons in the thalamus were osteoponti n -positive. The susceptibility to seizures of OPN-/- and OPN+/+ mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine-induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA-induced cell death in OPN-/- mouse neuronal cultures. Conclusion: We demonstrated that osteopontin is up-regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in degenerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3 days after SE.