Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Neuroprotective effects of gelsolin during murine stroke
Matthias Endres, … , David J. Kwiatkowski, Michael A. Moskowitz
Matthias Endres, … , David J. Kwiatkowski, Michael A. Moskowitz
Published February 1, 1999
Citation Information: J Clin Invest. 1999;103(3):347-354. https://doi.org/10.1172/JCI4953.
View: Text | PDF
Article Article has an altmetric score of 3

Neuroprotective effects of gelsolin during murine stroke

  • Text
  • PDF
Abstract

Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury following brain ischemia. The activity of these channels is modulated by dynamic changes in the actin cytoskeleton, which may occur, in part, through the actions of the actin filament–severing protein gelsolin. We show that gelsolin-null neurons have enhanced cell death and rapid, sustained elevation of Ca2+ levels following glucose/oxygen deprivation, as well as augmented cytosolic Ca2+ levels in nerve terminals following depolarization in vitro. Moreover, major increases in infarct size are seen in gelsolin-null mice after reversible middle cerebral artery occlusion, compared with controls. In addition, treatment with cytochalasin D, a fungal toxin that depolymerizes actin filaments, reduced the infarct size of both gelsolin-null and control mice to the same final volume. Hence, enhancement or mimicry of gelsolin activity may be neuroprotective during stroke.

Authors

Matthias Endres, Klaus Fink, Jinmin Zhu, Nancy E. Stagliano, Vimala Bondada, James W. Geddes, Toshifumi Azuma, Mark P. Mattson, David J. Kwiatkowski, Michael A. Moskowitz

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Neuronal vulnerability to combined glucose and oxygen deprivation is inc...
Neuronal vulnerability to combined glucose and oxygen deprivation is increased in hippocampal neurons lacking gelsolin (gsn). Cultures from gsn+/+, gsn+/–, and gsn–/– mice were subjected to combined G/O deprivation or medium change without G/O deprivation (control) for 30 min. Cultures were then incubated for an additional 20 h in Locke's solution and neuronal survival was quantified. Values are the mean and SE of determinations made in four separate cultures. *P < 0.05 compared with the value in gsn+/+ cultures exposed to G/O deprivation. **P < 0.01 compared with value in gsn+/+ cultures exposed to G/O deprivation, and P < 0.05 compared with the value in gsn+/– cultures exposed to G/O deprivation. ANOVA followed by Scheffe's post hoc tests. G/O, glucose/oxygen.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 patents
35 readers on Mendeley
See more details