The effects of superoxide dismutase mimetic MnTMPyP on the altered blood–brain barrier integrity in experimental preeclampsia with or without seizures in rats

Orhan, Nurcan; Yılmaz, Canan Uğur; Ekizoğlu, Oğuzhan; Ahıshalı, Bülent; Arıcan, Nadir; Küçük, Mutlu; Elmas, İmdat; Gürses, Candan; Kalayci, Rivaze; Kaya, Mehmet

doi:10.1016/j.brainres.2014.03.029

Cited by 8 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with other reports on TJ-independent mechanisms of BBB breakdown [30, 52, 57], the present analyses reveal that claudin 5- and occludin-positive TJ strands remain detectable in each of the investigated time points (Fig. 1, Additional file 1: Figure S2).…”

Section: Discussionsupporting

confidence: 92%

Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia

Krueger

Mages

Hobusch

et al. 2019

acta neuropathol commun

View full text Add to dashboard Cite

In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO. Thereby, BBB breakdown correlated with alterations of the endothelial surface, indicated by a discontinuous isolectin-B4 staining, while tight junction strands remained detectable using electron and immunofluorescence microscopy. Noteworthy, already 30 min after MCAO, up to 60% of the ischemia-affected vessels showed an endothelial edema, paralleled by edematous astrocytic endfeet, clearly preceding FITC-albumin extravasation. With increasing ischemic periods, scores of vascular damage significantly increased with up to 60% of the striatal vessels showing loss of endothelial integrity. Remarkably, comparison of permanent and transient ischemia did not provide significant differences 4 h after ischemia induction. As these degenerations also involved penumbral areas of potentially salvageable tissue, adjuvant approaches of endothelial protection may help to reduce the vasogenic edema after ischemic stroke.Electronic supplementary materialThe online version of this article (10.1186/s40478-019-0671-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 92%

Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia

Krueger

Mages

Hobusch

et al. 2019

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

“…However, over the years, reports of increased transport over the BBB without obvious associated changes in interendothelial junctions have been accumulating, suggesting that TJ-independent processes may contribute to BBB permeability changes in many occasions. An increase in the number of cytoplasmic vesicles in BBB endothelium in vivo has been associated with cortical cold injury (Nag et al, 2007), contusion injury , seizure activity (Gurses et al, 2013;Kaya et al, 2013;Orhan et al, 2014), pre-and postnatal stress (Gomez-Gonzalez et al, 2011;Sharma et al, 1995), hyperbaric oxygen treatment , sepsis (Esen et al, 2012;Kaya and Ahishali, 2011), and methamphetamine abuse (Martins et al, 2013). Most evidence for the involvement of vesicular transcytosis in BBB failure comes from the hypoxic/ischemic brain (Cipolla et al, 2004;Ito et al, 1980;Kaur et al, 2006;Knowland et al, 2014;Krueger et al, 2013Krueger et al, , 2015Plateel et al, 1997;Reeson et al, 2015) (Table 2).…”

Section: Evidence For a Transcellular Route Across The Bbb In Patholomentioning

confidence: 99%

“…These drugs inhibit dopamine and serotonine transporters and release monoamines at the synapse, inducing the phosphorylation of eNOS that is linked to increased expression of Cav1 and endocytosis (Martins et al, ). MnTMPyP (manganese(III) tetrakis(1‐methyl‐4‐pyridyl)porphyrin), a superoxide dismutase (SOD) mimetic that scavenges free radicals was shown to prevent endocytosis of HRP induced by pre‐eclampsia and pentylenetetrazol (Orhan et al, ).…”

Section: Vesicular Bbb Transport and Ca2+ Signalingmentioning

confidence: 99%

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Bock

Haver

Vandenbroucke

et al. 2016

Glia

127

100

View full text Add to dashboard Cite

Efficient neuronal signaling in the central nervous system strictly depends on a well-balanced microenvironment around glial cells, synapses, and axons. Unique features of the blood-brain barrier (BBB) endothelium largely determine the composition of this micro-milieu and are dependent on the tight interplay with surrounding astrocytes and pericytes. BBB endothelial cells are endowed with a highly restrictive junctional complex that occludes the intercellular cleft, thereby preventing paracellular diffusion. The paracellular pathway is subject to extensive research as integrity loss of the junctional complex is associated with many neuropathologies, inflammation, and edema. Another important feature of the BBB endothelium is the low prevalence of nonspecific, transcytotic events, including (macro)pinocytosis, clathrin-dependent and caveolin-dependent endocytosis and the subsequent trafficking of vesicles to the opposite membrane. Although less studied, evidence is accruing that this pathway importantly contributes to increased BBB permeability, often when the junctional complex remains intact. Here, we review current knowledge on the contribution of the transcellular pathway to the BBB leak observed in different pathologic conditions. In addition, we hypothesize that nonselective, large pore connexin and pannexin channels may contribute to transcellular transport, either by providing a direct diffusion pathway across the endothelial monolayer, or indirectly, by exerting control over intracellular levels of the signaling ion Ca(2+) that is involved in many steps of the vesicular pathway. We conclude that transcytotic events at the BBB, despite being less acknowledged, cannot be simply dismissed as done in the past, but actively contribute to BBB leakage in many different pathologies. GLIA 2016;64:1097-1123.

show abstract

“…Prior to eclampsia, patients usually develop an intensified peripheral inflammatory response along with dysfunctional blood brain barrier. The latter event facilitates the entrance of inflammatory mediators and cells leading to enhanced activity of microglia, which are macrophage like cells in the brain and neuroinflammation [10,210]. The exaggerated neuroinflammatory response leads to neural loss, hippocampal lesions and amplification of neuronal excitability, and consequent seizure outbreak.…”

Section: Cap Mitigates Central Neuroinflammationmentioning

confidence: 99%

Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

Wedn

El-Bassossy

Eid

et al. 2021

Biochemical Pharmacology

View full text Add to dashboard Cite

The effects of superoxide dismutase mimetic MnTMPyP on the altered blood–brain barrier integrity in experimental preeclampsia with or without seizures in rats

Cited by 8 publications

References 51 publications

Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia

Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

Contact Info

Product

Resources

About