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The effects of superoxide dismutase mimetic MnTMPyP on the altered blood-brain barrier integrity in experimental preeclampsia with or without seizures in rats.
- Source :
-
Brain research [Brain Res] 2014 May 14; Vol. 1563, pp. 91-102. Date of Electronic Publication: 2014 Mar 25. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Blood-Brain Barrier metabolism
Blood-Brain Barrier pathology
Cerebral Cortex metabolism
Cerebral Cortex ultrastructure
Female
Hippocampus metabolism
Hippocampus ultrastructure
Occludin metabolism
Pregnancy
Rats
Rats, Sprague-Dawley
Seizures complications
Blood-Brain Barrier drug effects
Metalloporphyrins pharmacology
Pre-Eclampsia metabolism
Seizures metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1563
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 24680906
- Full Text :
- https://doi.org/10.1016/j.brainres.2014.03.029