title: Endothelial NOS activation induces the blood-brain barrier disruption via ER stress following status epilepticus.
abstract: The blood-brain barrier (BBB) maintains the unique brain microenvironment, which is separated from the systemic circulating system. Since the endoplasmic reticulum (ER) is an important cell organelle that is responsible for protein synthesis, the correct folding and sorting of proteins contributing to cell survivals, ER stress is a potential cause of cell damage in various diseases. Therefore, it would be worthy to explore the the relationship between the ER stress and BBB disruption during vasogenic edema formation induced by epileptogenic insults. In the present study, we investigated the roles of ER stress in vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced status epilepticus (SE). SE-induced eNOS activation induces BBB breakdown via up-regulation of GRP78 expression and dysfunction of SMI-71 (an endothelial BBB marker) in the piriform cortex (PC). In addition, caveolin-1 peptide (an eNOS inhibitor) effectively attenuated GRP78 expression and down-regulation of SMI-71. Taken together, our findings suggest that eNOS-mediated ER stress may participate in SE-induced vasogenic edema formation. Therefore, the modulation of ER stress may be a considerable strategy for therapy in impairments of endothelial cell function.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200702, South Korea.
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Ko
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200702, South Korea.
authors.forename: Ji Yang
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200702, South Korea.
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Hyun
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200702, South Korea. Electronic address: jieunkim@hallym.ac.kr.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D051242:Caveolin 1 / Q000008:administration & dosage; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010862:Pilocarpine; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D051242:Caveolin 1; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D052250:Nitric Oxide Synthase Type III; D010862:Pilocarpine; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C496316:Nos3 protein, rat
keywords: Endoplasmic reticulum stress; GRP78; SMI-71; Status epilepticus; Vasogenic edema; eNOS