English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport

Spieth, L., Berghoff, S. A., Stumpf, S. K., Winchenbach, J., Michaelis, T., Watanabe, T., et al. (2021). Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport. Neuro-Oncology Advances, 3(1): vdab140. doi:10.1093/noajnl/vdab140.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
3395263.pdf (Publisher version), 2MB
Name:
3395263.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-

Locators

show

Creators

show
hide
 Creators:
Spieth, L., Author
Berghoff, S. A., Author
Stumpf, S. K., Author
Winchenbach, J., Author
Michaelis, T.1, Author           
Watanabe, T.1, Author           
Gerndt, N., Author
Düking, T., Author
Hofer, S.1, Author           
Ruhwedel, T., Author
Shaib, A. H., Author
Willig, K., Author
Frahm, J.1, Author           
Rhee, J. S., Author
Minguet, S., Author
Möbius, W., Author
Kruse, N., Author
von der Brelie, C., Author
Michels, P., Author
Stadelmann, C., Author
Hülper, P., AuthorSaher, G., Author more..
Affiliations:
1Biomedical NMR Research GmbH, MPI for biophysical chemistry, Max Planck Society, ou_578634              

Content

show
hide
Free keywords: blood brain barrier; chemotherapy; drug delivery; general anesthesia; glioblastoma
 Abstract: Abstract Background: Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood-brain barrier (BBB). To induce clinical anesthesia, general anesthetics such as isoflurane readily penetrate the BBB. Here, we investigated whether isoflurane can be utilized for therapeutic drug delivery. Methods: Barrier function in primary endothelial cells was evaluated by transepithelial/transendothelial electrical resistance, and nanoscale STED and SRRF microscopy. In mice, BBB permeability was quantified by extravasation of several fluorescent tracers. Mouse models including the GL261 glioma model were evaluated by MRI, immunohistochemistry, electron microscopy, western blot, and expression analysis. Results: Isoflurane enhances BBB permeability in a time- and concentration-dependent manner. We demonstrate that, mechanistically, isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport in brain endothelial cells. BBB tightness re-establishes directly after termination of anesthesia, providing a defined window for drug delivery. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy. Conclusions: Combination therapy, involving isoflurane-mediated BBB permeation with drug administration has far-reaching therapeutic implications for CNS malignancies.

Details

show
hide
Language(s): eng - English
 Dates: 2021-09-20
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1093/noajnl/vdab140
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : -
Grant ID : SPP1759
Funding program : -
Funding organization : DFG
Project name : -
Grant ID : SA2114/2-2
Funding program : -
Funding organization : DFG
Project name : -
Grant ID : 2019.138.1
Funding program : -
Funding organization : Wilhelm-Sander-Stiftung
Project name : -
Grant ID : -
Funding program : European Research Council Advanced Grant
Funding organization : European Research Council
Project name : SFB1160
Grant ID : B01
Funding program : -
Funding organization : DFG
Project name : -
Grant ID : 431460824
Funding program : (CRC1450)
Funding organization : DFG

Source 1

show
hide
Title: Neuro-Oncology Advances
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 13 Volume / Issue: 3 (1) Sequence Number: vdab140 Start / End Page: - Identifier: -