Počet záznamů: 1
The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury
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SYSNO ASEP 0566939 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury Tvůrce(i) Suchá, Petra (UEM-P)
Heřmanová, Zuzana (UEM-P) ORCID
Chmelová, Martina (UEM-P)
Kirdajová, Denisa (UEM-P) RID, ORCID
Garcia, Camacho, Sara (UEM-P)
Marchetti, Valeria (UEM-P)
Voříšek, Ivan (UEM-P)
Turečková, Jana (UEM-P) ORCID
Shany, E. (CZ)
Jirák, D. (CZ)
Anděrová, Miroslava (UEM-P) RID, ORCID
Vargová, Lýdia (UEM-P) RIDČíslo článku 1054919 Zdroj.dok. Frontiers in Cellular Neuroscience. - : Frontiers Media
Roč. 16, dec. (2022)Poč.str. 19 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova TRPV4 ; AQP4 ; ECS diffusion ; MRI ; cerebral ischemia ; brain edema Obor OECD Neurosciences (including psychophysiology CEP GA20-05770S GA ČR - Grantová agentura ČR EF15_003/0000419 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UEM-P - RVO:68378041 UT WOS 000899856500001 EID SCOPUS 85144896036 DOI 10.3389/fncel.2022.1054919 Anotace IntroductionAstrocytic Aquaporin 4 (AQP4) and Transient receptor potential vanilloid 4 (TRPV4) channels form a functional complex that likely influences cell volume regulation, the development of brain edema, and the severity of the ischemic injury. However, it remains to be fully elucidated whether blocking these channels can serve as a therapeutic approach to alleviate the consequences of having a stroke. Methods and resultsIn this study, we used in vivo magnetic resonance imaging (MRI) to quantify the extent of brain lesions one day (D1) and seven days (D7) after permanent middle cerebral artery occlusion (pMCAO) in AQP4 or TRPV4 knockouts and mice with simultaneous deletion of both channels. Our results showed that deletion of AQP4 or TRPV4 channels alone leads to a significant worsening of ischemic brain injury at both time points, whereas their simultaneous deletion results in a smaller brain lesion at D1 but equal tissue damage at D7 when compared with controls. Immunohistochemical analysis 7 days after pMCAO confirmed the MRI data, as the brain lesion was significantly greater in AQP4 or TRPV4 knockouts than in controls and double knockouts. For a closer inspection of the TRPV4 and AQP4 channel complex in the development of brain edema, we applied a real-time iontophoretic method in situ to determine ECS diffusion parameters, namely volume fraction (alpha) and tortuosity (lambda). Changes in these parameters reflect alterations in cell volume, and tissue structure during exposure of acute brain slices to models of ischemic conditions in situ, such as oxygen-glucose deprivation (OGD), hypoosmotic stress, or hyperkalemia. The decrease in alpha was comparable in double knockouts and controls when exposed to hypoosmotic stress or hyperkalemia. However, during OGD, there was no decrease in alpha in the double knockouts as observed in the controls, which suggests less swelling of the cellular components of the brain. ConclusionAlthough simultaneous deletion of AQP4 and TRPV4 did not improve the overall outcome of ischemic brain injury, our data indicate that the interplay between AQP4 and TRPV4 channels plays a critical role during neuronal and non-neuronal swelling in the acute phase of ischemic injury. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2023 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fncel.2022.1054919/full
Počet záznamů: 1