Reorganization of gap junctions after focused ultrasound blood-brain barrier opening in the rat brain

• Verfasst von: Alonso, Angelika [VerfasserIn]
• Verfasst von: Reinz, Eileen [VerfasserIn]
• Verfasst von: Jenne, Jürgen [VerfasserIn]
• Verfasst von: Fatar, Marc [VerfasserIn]
• Verfasst von: Schmidt-Glenewinkel, Hannah [VerfasserIn]
• Verfasst von: Hennerici, Michael G. [VerfasserIn]
• Verfasst von: Meairs, Stephen [VerfasserIn]
• Titel: Reorganization of gap junctions after focused ultrasound blood-brain barrier opening in the rat brain
• Verf.angabe: Angelika Alonso, Eileen Reinz, Jürgen W. Jenne, Marc Fatar, Hannah Schmidt-Glenewinkel, Michael G. Hennerici and Stephen Meairs
• E-Jahr: 2010
• Jahr: [2010]
• Umfang: 9 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 12.03.2021
• Titel Quelle: Enthalten in: Journal of cerebral blood flow & metabolism
• Ort Quelle: Thousands Oaks, Calif. : Sage, 1981
• Jahr Quelle: 2010
• Band/Heft Quelle: 30(2010), 7, Seite 1394-1402
• ISSN Quelle: 1559-7016
• DOI: doi:10.1038/jcbfm.2010.41
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: blood-brain barrier
• Sach-SW: Connexin 36
• Sach-SW: Connexin 43
• Sach-SW: gap junctions
• Sach-SW: microbubbles
• Sach-SW: ultrasound
• K10plus-PPN: 1751211673

Abstract

Ultrasound-induced opening of the blood-brain barrier (BBB) is an emerging technique for targeted drug delivery to the central nervous system. Gap junctions allow transfer of information between adjacent cells and are responsible for tissue homeostasis. We examined the effect of ultrasound-induced BBB opening on the structure of gap junctions in cortical neurons, expressing Connexin 36, and astrocytes, expressing Connexin 43, after focused 1-MHz ultrasound exposure at 1.25 MPa of one hemisphere together with intravenous microbubble (Optison, Oslo, Norway) application. Quantification of immunofluorescence signals revealed that, compared with noninsonicated hemispheres, small-sized Connexin 43 and 36 gap-junctional plaques were markedly reduced in areas with BBB breakdown after 3 to 6 hours (34.02±6.04% versus 66.49±2.16%, P=0.02 for Connexin 43; 33.80±1.24% versus 36.77±3.43%, P=0.07 for Connexin 36). Complementing this finding, we found significant increases in large-sized gap-junctional plaques (5.76±0.96% versus 1.02±0.84%, P=0.05 for Connexin 43; 5.62±0.22% versus 4.65±0.80%, P=0.02 for Connexin 36). This effect was reversible at 24 hours after ultrasound exposure. Western blot analyses did not show any change in the total connexin amount. These results indicate that ultrasound-induced BBB opening leads to a reorganization of gap-junctional plaques in both neurons and astrocytes. The plaque-size increase may be a cellular response to imbalances in extracellular homeostasis after BBB leakage.