Characterization of osteopontin expression and function after status epilepticus.
OBJECTIVE
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 immunohistochemistry. 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 osteopontin-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.


CONCLUSIONS
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.
Borges
Karin
K
Department of Pharmaceutical Sciences, Texas Tech Health Sciences Center, Amarillo, Texas 79106, USA. karin.borges@ttuhsc.edu
Gearing
Marla
M
Rittling
Susan
S
Sorensen
Esben S
ES
Kotloski
Robert
R
Denhardt
David T
DT
Dingledine
Raymond
R
D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005481:Flurothyl / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010862:Pilocarpine / Q000009:adverse effects; D016548:Prosencephalon / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D013226:Status Epilepticus / Q000209:etiology / Q000235:genetics / Q000378:metabolism*
D039481:CD11b Antigen; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D010862:Pilocarpine; D053495:Osteopontin; D016202:N-Methylaspartate; D005481:Flurothyl; D052247:Nitric Oxide Synthase Type II