title: Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway.
abstract: The blood-brain barrier (BBB) disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process. However, the signaling pathway concerning vasogenic edema formation has not been clarified. In the present study, status epilepticus (SE) resulted in vascular endothelial growth factor (VEGF) over-expression accompanied by loss of BBB integrity in the rat piriform cortex. Leptomycin B (LMB, an inhibitor of chromosome region maintenance 1) attenuated SE-induced vasogenic edema formation. This anti-edema effect of LMB was relevant to inhibitions of VEGF over-expression as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, SB202190 (a p38 MAPK inhibitor) ameliorated vasogenic edema and VEGF over-expression induced by SE. These findings indicate that p38 MAPK/VEGF signaling pathway may be involved in BBB disruption following SE. Thus, we suggest that p38 MAPK/VEGF axis may be one of therapeutic targets for vasogenic edema in various neurological diseases.
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, South Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, South Korea; Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Su-Ji
authors.initials: SJ
authors.lastname: Min
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, South Korea; Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, South Korea; Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, South Korea; Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea. Electronic address: tckang@hallym.ac.kr.
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010862:Pilocarpine; D066195:Piriform Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D010862:Pilocarpine; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C038753:leptomycin B
keywords: Epilepsy; Leptomycin B; P38 MAPK; Piriform cortex; Seizure; VEGF