caa a22 4500 606201238 CHVBK 20210128100947.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0632-5 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0632-5 Extracellular signal-regulated kinase1/2-dependent changes in tight junctions after ischemic preconditioning contributes to tolerance induction after ischemic stroke [Elektronische Daten] [Jin Shin, Yul Kim, Sae Jeong, Kyung-Eun Lee, Hee-Sun Kim, Eun-Mi Park] Less disruption of the blood-brain barrier (BBB) after severe ischemic stroke is one of the beneficial outcomes of ischemic preconditioning (IP). However, the effect of IP on tight junctions (TJs), which regulate paracellular permeability of the BBB, is not well understood. In the present study, we examined IP-induced changes in TJs before and after middle cerebral artery occlusion (MCAO) in mice, and the association between changes in TJs and tolerance to a subsequent insult. After IP, we found decreased levels of transmembrane TJ proteins occludin and claudin-5, and widened gaps of TJs with perivascular swelling at the ultrastructural level in the brain. An inflammatory response was also observed. These changes were reversed by inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) via the specific ERK1/2 inhibitor U0126. After MCAO, reduced brain edema and inflammatory responses were associated with altered levels of angiogenic factors and cytokines in preconditioned brains. Pretreatment with U0126 reversed the neuroprotective effects of IP against MCAO. These findings suggest that ERK1/2 activation has a pivotal role in IP-induced changes in TJs and inflammatory response, which serve to protect against BBB breakdown and inflammation after ischemic stroke. Springer-Verlag Berlin Heidelberg, 2013 Blood-brain barrier nationallicence ERK1/2 nationallicence Ischemic preconditioning nationallicence Ischemic stroke nationallicence Tight junction proteins nationallicence U0126 nationallicence Shin Jin Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut Kim Yul Department of Pharmacology, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut Jeong Sae Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut Lee Kyung-Eun Department of Pharmacology, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut Kim Hee-Sun Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Seoul, Republic of Korea aut Park Eun-Mi Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 13-26 1863-2653 220:1<13 2015 220 429 https://doi.org/10.1007/s00429-013-0632-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0632-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shin Jin Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Yul Department of Pharmacology, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Jeong Sae Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Kyung-Eun Department of Pharmacology, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Hee-Sun Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Park Eun-Mi Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, 158-710, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 13-26 1863-2653 220:1<13 2015 220 429