We investigated the effects of a cell-permeable
superoxide dismutase mimetic,
manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (
MnTMPyP) on blood-brain barrier (BBB) integrity following
pentylenetetrazole (PTZ)-induced
seizures in experimental
preeclampsia symptoms induced by
N(omega)-nitro-l-arginine methyl ester (
l-NAME) in pregnant rats. To show the functional and morphological alterations in BBB integrity, quantitative analysis of
sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopic assessment of
horseradish peroxidase (HRP) permeability were performed. Varying degrees of
proteinuria were seen and arterial blood pressure increased in
l-NAME-treated pregnant rats (p<0.01).
MnTMPyP pretreatment and convulsive PTZ challenge significantly decreased the immunoreactivity of
occludin in hippocampal capillaries in
l-NAME-treated pregnant rats (p<0.01). BBB permeability to NaFlu significantly increased in pregnant rats treated with
l-NAME plus PTZ (p<0.01), but
MnTMPyP pretreatment did not significantly decrease NaFlu penetration into the brain parenchyma in these animals. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in the capillary endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated with
l-NAME and
l-NAME plus PTZ with the abundance being more in the latter group.
MnTMPyP pretreatment caused a marked reduction in the frequency of HRP reaction product containing vesicles in both experimental settings. In conclusion, the results of the present study provide evidence that
MnTMPyP plays an important role in limiting the enhanced vesicle-mediated transcellular transport in BBB endothelium in a rat model of
preeclampsia and the differences in the way of transports of NaFlu and HRP might be responsible for the different effects of
MnTMPyP on the BBB permeability to these two tracers.