Neuroprotective effects of gelsolin during murine stroke

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)347-354
Number of pages8
JournalJournal of Clinical Investigation
Volume103
Issue number3
StatePublished - Feb 1999
Externally publishedYes

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Gelsolin
Neuroprotective Agents
Stroke
Actin Cytoskeleton
Cytochalasin D
Mycotoxins
Middle Cerebral Artery Infarction
N-Methyl-D-Aspartate Receptors
Brain Ischemia
Cell Death
Oxygen
Neurons
Glucose
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Endres, M., Fink, K., Zhu, J., Stagliano, N. E., Bondada, V., Geddes, J. W., ... Moskowitz, M. A. (1999). Neuroprotective effects of gelsolin during murine stroke. Journal of Clinical Investigation, 103(3), 347-354.

Neuroprotective effects of gelsolin during murine stroke. / Endres, Matthias; Fink, Klaus; Zhu, Jinmin; Stagliano, Nancy E.; Bondada, Vimala; Geddes, James W.; Azuma, Toshifumi; Mattson, Mark P.; Kwiatkowski, David J.; Moskowitz, Michael A.

In: Journal of Clinical Investigation, Vol. 103, No. 3, 02.1999, p. 347-354.

Research output: Contribution to journalArticle

Endres, M, Fink, K, Zhu, J, Stagliano, NE, Bondada, V, Geddes, JW, Azuma, T, Mattson, MP, Kwiatkowski, DJ & Moskowitz, MA 1999, 'Neuroprotective effects of gelsolin during murine stroke', Journal of Clinical Investigation, vol. 103, no. 3, pp. 347-354.
Endres M, Fink K, Zhu J, Stagliano NE, Bondada V, Geddes JW et al. Neuroprotective effects of gelsolin during murine stroke. Journal of Clinical Investigation. 1999 Feb;103(3):347-354.
Endres, Matthias ; Fink, Klaus ; Zhu, Jinmin ; Stagliano, Nancy E. ; Bondada, Vimala ; Geddes, James W. ; Azuma, Toshifumi ; Mattson, Mark P. ; Kwiatkowski, David J. ; Moskowitz, Michael A. / Neuroprotective effects of gelsolin during murine stroke. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 3. pp. 347-354.
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AU - Geddes, James W.

AU - Azuma, Toshifumi

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