title: The effects of superoxide dismutase mimetic MnTMPyP on the altered blood-brain barrier integrity in experimental preeclampsia with or without seizures in rats.
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.
authors.affiliation: Department of Neurosciences, The Institute of Experimental Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Orhan
authors.affiliation: Department of Laboratory Animal Biology and Biomedical Application Techniques, The Institute of Experimental Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Ugur Yilmaz
authors.affiliation: Sadi Konuk Training and Research Hospital, Bakirkoy, Istanbul, Turkey.
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Ekizoglu
authors.affiliation: Department of Histology and Embryology, Istanbul Faculty of Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Ahishali
authors.affiliation: Department of Forensic Medicine, Istanbul Faculty of Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.affiliation: Department of Laboratory Animal Biology and Biomedical Application Techniques, The Institute of Experimental Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.affiliation: Department of Forensic Medicine, Istanbul Faculty of Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Imdat
authors.initials: I
authors.lastname: Elmas
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Candan
authors.initials: C
authors.lastname: Gürses
authors.affiliation: Department of Laboratory Animal Biology and Biomedical Application Techniques, The Institute of Experimental Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey.
authors.forename: Rivaze
authors.initials: R
authors.lastname: Kalayci
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey. Electronic address: mehkaya@istanbul.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D008665:Metalloporphyrins / Q000494:pharmacology*; D062793:Occludin / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000378:metabolism*
chemical_list: D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D062793:Occludin; C568987:Ocln protein, rat
keywords: Blood–brain barrier; Electron microscopy; Horseradish peroxidase; MnTMPyP; Preeclampsia; Seizure; Sodium fluorescein