title: Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke.
abstract: BACKGROUND
  Electroacupuncture (EA) is a modern application based on combination of traditional manual acupuncture and electrotherapy that is frequently recommended as an adjuvant treatment for ischemic stroke. EA preconditioning can ameliorate blood-brain barrier (BBB) dysfunction and brain edema in ischemia-reperfusion injury; however, its mechanism remains unclear. This study investigated the preventive effects of EA preconditioning, particularly on BBB injury, followed by a transient middle cerebral artery occlusion (MCAO) model in mice.
  
  
  RESULTS
  Mice were treated with EA (20 min) at Baihui (GV20) and Dazhui (GV14) acupoints once a day for 3 days before ischemic injury. Infarct volume, neurological deficits, oxidative stress, Evans blue leakage and brain edema were evaluated at 24 h after ischemia-reperfusion injury. EA preconditioning significantly decreased infarct volume and improved neurological function even after ischemic injury. In addition, both Evans blue leakage and water content were significantly reduced in EA preconditioned mice. Whereas the expression of tight junction proteins, ZO-1 and claudin-5, were remarkably increased by EA preconditioning. Mice with EA preconditioning showed the reduction of astrocytic aquaporin 4, which is involved in BBB permeabilization. In addition, we found that EA preconditioning decreased reactive oxygen species (ROS) in brain tissues after ischemic injury. The expression of NADPH oxidase 4 (NOX4), not NOX2, was significantly suppressed in EA preconditioned mice.
  
  
  CONCLUSIONS
  These results suggest that EA preconditioning improve neural function after ischemic injury through diminishing BBB disruption and brain edema. And, the reduction of ROS generation and NOX4 expression by EA preconditioning might be involved in BBB recovery. Therefore, EA may serve as a potential preventive strategy for patients at high risk of ischemic stroke.
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.
authors.forename: Yeon Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.|Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.|Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.
authors.forename: Hyung Bum
authors.initials: HB
authors.lastname: Seo
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.|Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea. julie@pusan.ac.kr.|Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea. julie@pusan.ac.kr.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 626-870, Republic of Korea. julie@pusan.ac.kr.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation; D015671:Electroacupuncture; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse