scholarly journals The Regional Specific Alterations in BBB Permeability are Relevant to the Differential Responses of 67-kDa LR Expression in Endothelial Cells and Astrocytes Following Status Epilepticus

2019 ◽  
Vol 20 (23) ◽  
pp. 6025 ◽  
Author(s):  
Hana Park ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Vasogenic Edema ◽  
Molecular Layer ◽  
Piriform Cortex ◽  
Laminin Receptor ◽  
Edema Formation ◽  
Western Blots ◽  
Expression Levels ◽  
Prolonged Seizure ◽  
Hippocampus Proper

Status epilepticus (a prolonged seizure activity, SE) differently affects vasogenic edema formation and dystrophin-aquaporin 4 (AQP4) expressions between the rat hippocampus and the piriform cortex (PC). In the present study, we explored whether the 67-kDa laminin receptor (LR) expression was relevant to the regional specific susceptibility of vasogenic edema at 3 days after SE. In spite of no difference in expression levels of 67-kDa LR, dystrophin, and AQP4 under physiological conditions, SE-induced serum extravasation was more severe in the PC than the hippocampus. Western blots demonstrated that SE reduced expression levels of 67-kDa LR, dystrophin, and AQP4 in the PC, but not in the hippocampus proper. Immunofluorescent studies revealed that SE increased 67-kDa LR expression in reactive CA1 astrocyte, but reduced it in the PC and the molecular layer of the dentate gyrus due to massive astroglial loss. Furthermore, SE decreased expressions of endothelial 67-kDa LR and SMI-71 (endothelial brain barrier antigen) in these regions. The 67-kDa LR neutralization evoked serum extravasation in these regions of normal animals without astroglial loss. Similar to SE, 67-kDa LR neutralization also reduced dystrophin-AQP4 expressions in the PC more than the total hippocampus. Furthermore, 67-kDa LR IgG infusion increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not c-Jun N-terminal kinase, independent of phosphoprotein enriched in astrocytes of 15 kDa (PEA15) activity. Co-treatment of U0126 (an ERK1/2 inhibitor) alleviated vasogenic edema formation and the reduced dystrophin-AQP4 expressions induced by 67-kDa LR neutralization. The 67-kDa LR IgG infusion also increased the susceptibility to SE induction. Therefore, our findings suggested that the cellular specific alterations in 67-kDa LR expression might be involved in the severity of SE-induced vasogenic edema formation in regional specific manners, which might affect the susceptibility to SE induction.

scholarly journals Epigallocatechin-3-Gallate and PEDF 335 Peptide, 67LR Activators, Attenuate Vasogenic Edema, and Astroglial Degeneration Following Status Epilepticus

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 854
Author(s):  
Ji-Eun Kim ◽  
Hana Park ◽  
Min-Jeong Jeong ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Vasogenic Edema ◽  
Pigment Epithelium ◽  
Piriform Cortex ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Laminin Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Edema Formation ◽  
Aqp4 Expression ◽  
Underlying Mechanisms

Non-integrin 67-kDa laminin receptor (67LR) is involved in cell adherence to the basement membrane, and it regulates the interactions between laminin and other receptors. The dysfunction of 67LR leads to serum extravasation via blood-brain barrier (BBB) disruption. Polyphenol (–)-epigallocatechin-3-O-gallate (EGCG) and pigment epithelium-derived factor (PEDF) bind to 67LR and inhibit neovascularization. Therefore, in the present study, we investigated the effects of EGCG and NU335, a PEDF-derive peptide, on BBB integrity and their possible underlying mechanisms against vasogenic edema formation induced by status epilepticus (SE, a prolonged seizure activity). Following SE, both EGCG and NU335 attenuated serum extravasation and astroglial degeneration in the rat piriform cortex (PC). Both EGCG and NU335 reversely regulated phosphatidylinositol 3 kinase (PI3K)/AKT–eNOS (endothelial nitric oxide synthase) mediated BBB permeability and aquaporin 4 (AQP4) expression in endothelial cells and astrocytes through the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways, respectively. Furthermore, EGCG and NU335 decreased p47Phox (a nicotinamide adenine dinucleotide phosphate oxidase subunit) expression in astrocytes under physiological and post-SE conditions. Therefore, we suggest that EGCG and PEDF derivatives may activate 67LR and its downstream effectors, and they may be considerable anti-vasogenic edema agents.

Up-regulation of endothelial endothelin-1 expression prior to vasogenic edema formation in the rat piriform cortex following status epilepticus

2011 ◽  
Vol 501 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Seung-Mook Jo ◽  
Hea Jin Ryu ◽  
Ji-Eun Kim ◽  
Seong-Il Yeo ◽  
Min-Ju Kim ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Vasogenic Edema ◽  
Piriform Cortex ◽  
Edema Formation ◽  
Endothelin 1

Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus

2010 ◽  
Vol 518 (22) ◽  
pp. 4612-4628 ◽  
Author(s):  
Ji-Eun Kim ◽  
Seong-Il Yeo ◽  
Hea Jin Ryu ◽  
Min-Ju Kim ◽  
Duk-Soo Kim ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Piriform Cortex ◽  
Edema Formation

scholarly journals CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus

2019 ◽  
Vol 20 (19) ◽  
pp. 4862 ◽  
Author(s):  
Min-Ju Kim ◽  
Hana Park ◽  
Seo-Hyeon Choi ◽  
Min-Jeong Kong ◽  
Ji-Eun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Status Epilepticus ◽  
Vasogenic Edema ◽  
Acid Methyl Ester ◽  
Nuclear Factor Κb ◽  
Related Factor ◽  
Nuclear Factor ◽  
Edema Formation ◽  
Tnf Α ◽  
Nrf2 Expression

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that has anti-inflammatory, antioxidant, and neuroprotective activities. In the present study, we evaluate the effects of CDDO-Me on serum extravasation and astroglial death in the rat piriform cortex (PC) induced by status epilepticus (a prolonged seizure activity, SE) in order to propose an underlying pharmacological mechanism of CDDO-Me and its availability for treatment of vasogenic edema. CDDO-Me effectively mitigated serum extravasation and a massive astroglial loss in the PC following SE. CDDO-Me abrogated tumor necrosis factor-α (TNF-α) synthesis in activated microglia by inhibiting nuclear factor-κB (NF-κB) p65 serine 276 phosphorylation. CDDO-Me also abolished NF-κB threonine 435 phosphorylation in endothelial cells and TNF-α-mediated-phosphatidylinositol-3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling cascades, which trigger vasogenic edema following SE. Furthermore, CDDO-Me increased astroglial viability via the up-regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. Therefore, our findings suggest that CDDO-Me may ameliorate SE-induced vasogenic edema formation by regulating NF-κB p65 phosphorylations in microglia as well as endothelial cells and enhancing Nrf2 expression in astrocytes, respectively.

Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway

2016 ◽  
Vol 1651 ◽  
pp. 27-35 ◽  
Author(s):  
Duk-Soo Kim ◽  
Su-Ji Min ◽  
Min-Ju Kim ◽  
Ji-Eun Kim ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
P38 Mapk ◽  
Vasogenic Edema ◽  
Leptomycin B ◽  
Edema Formation ◽  
Vegf Pathway

scholarly journals Roscovitine Attenuates Microglia Activation and Monocyte Infiltration via p38 MAPK Inhibition in the Rat Frontoparietal Cortex Following Status Epilepticus

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 746 ◽  
Author(s):  
Ji-Eun Kim ◽  
Hana Park ◽  
Seo-Hyeon Choi ◽  
Min-Jeong Kong ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
P38 Mapk ◽  
Vasogenic Edema ◽  
Microglia Activation ◽  
Mitogen Activated Protein Kinase ◽  
Edema Formation ◽  
In Vivo Models ◽  
Frontoparietal Cortex ◽  
The Brain

Under physiological conditions, microglia are unique immune cells resident in the brain that is isolated from the systemic immune system by brain-blood barrier. Following status epilepticus (SE, a prolonged seizure activity), microglia are rapidly activated and blood-derived monocytes that infiltrate the brain; therefore, the regulations of microglia activation and monocyte infiltration are one of the primary therapeutic strategies for inhibition of undesirable consequences from SE. Roscovitine, a potent (but not selective) cyclin-dependent kinase 5 (CDK5) inhibitor, has been found to exert anti-inflammatory and microglia-inhibiting actions in several in vivo models, although the underlying mechanisms have not been clarified. In the present study, roscovitine attenuated SE-induces monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC), accompanied by reducing expressions of monocyte chemotactic protein-1 (MCP-1) and lysosome-associated membrane protein 1 (LAMP1) in resident microglia, while it did not affect microglia transformation to amoeboid form. Furthermore, roscovitine ameliorated the up-regulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, but not nuclear factor-κB-S276 phosphorylation. Similar to roscovitine, SB202190, a p38 MAPK inhibitor, mitigated monocyte infiltration and microglial expressions of MCP-1 and LAMP1 in the FPC following SE. Therefore, these findings suggest for the first time that roscovitine may inhibit SE-induced neuroinflammation via regulating p38 MAPK-mediated microglial responses.

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