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Rho kinase inhibition protects CA1 cells in organotypic hippocampal slices during in vitro ischemia.

Gisselsson, Lennart LU ; Toresson, Håkan LU ; Ruscher, Karsten LU and Wieloch, Tadeusz LU (2010) In Brain Research1966-01-01+01:00 1316. p.92-100
Abstract
The actin cytoskeleton is a dynamic superstructure that regulates multiple cellular functions and that has been implicated in cell death regulation. We investigated whether modulating the neuronal actin cytoskeleton polymerization by Rho GTPase kinase (ROCK) inhibition influences cell death in hippocampal neuronal cultures and in murine organotypic hippocampal slice cultures subjected to in vitro ischemia (IVI). During IVI, spines on vehicle treated hippocampal neurons collapsed and large dendritic actin aggregates were formed. Following ROCK inhibition by Y27632, the actin aggregates were markedly smaller while large filopodia extended from the dendritic trunk. Y27632 also provided strong neuroprotection of hippocampal pyramidal CA1... (More)
The actin cytoskeleton is a dynamic superstructure that regulates multiple cellular functions and that has been implicated in cell death regulation. We investigated whether modulating the neuronal actin cytoskeleton polymerization by Rho GTPase kinase (ROCK) inhibition influences cell death in hippocampal neuronal cultures and in murine organotypic hippocampal slice cultures subjected to in vitro ischemia (IVI). During IVI, spines on vehicle treated hippocampal neurons collapsed and large dendritic actin aggregates were formed. Following ROCK inhibition by Y27632, the actin aggregates were markedly smaller while large filopodia extended from the dendritic trunk. Y27632 also provided strong neuroprotection of hippocampal pyramidal CA1 neurons, which was of similar magnitude as protection by NMDA receptor blockade. Likewise, treatment with the F-actin depolymerizing agent latrunculin during IVI diminished actin aggregation and mitigated cell death following IVI. We propose that ROCK inhibition protects neurons against ischemic damage by disrupting actin polymerization thereby mitigating NMDA receptor induced toxicity and releasing ATP bound to actin for cellular energy use. We conclude that ROCK inhibitors abrogate multiple detrimental processes and could therefore be useful in stroke therapy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain Research1966-01-01+01:00
volume
1316
pages
92 - 100
publisher
Elsevier
external identifiers
  • wos:000275136200010
  • pmid:20026316
  • scopus:75349103034
ISSN
1872-6240
DOI
10.1016/j.brainres.2009.11.087
language
English
LU publication?
yes
id
57f41611-9cd4-486b-9c8b-d3c099c5adf1 (old id 1523408)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20026316?dopt=Abstract
date added to LUP
2010-01-11 17:01:20
date last changed
2018-05-29 11:49:58
@article{57f41611-9cd4-486b-9c8b-d3c099c5adf1,
  abstract     = {The actin cytoskeleton is a dynamic superstructure that regulates multiple cellular functions and that has been implicated in cell death regulation. We investigated whether modulating the neuronal actin cytoskeleton polymerization by Rho GTPase kinase (ROCK) inhibition influences cell death in hippocampal neuronal cultures and in murine organotypic hippocampal slice cultures subjected to in vitro ischemia (IVI). During IVI, spines on vehicle treated hippocampal neurons collapsed and large dendritic actin aggregates were formed. Following ROCK inhibition by Y27632, the actin aggregates were markedly smaller while large filopodia extended from the dendritic trunk. Y27632 also provided strong neuroprotection of hippocampal pyramidal CA1 neurons, which was of similar magnitude as protection by NMDA receptor blockade. Likewise, treatment with the F-actin depolymerizing agent latrunculin during IVI diminished actin aggregation and mitigated cell death following IVI. We propose that ROCK inhibition protects neurons against ischemic damage by disrupting actin polymerization thereby mitigating NMDA receptor induced toxicity and releasing ATP bound to actin for cellular energy use. We conclude that ROCK inhibitors abrogate multiple detrimental processes and could therefore be useful in stroke therapy.},
  author       = {Gisselsson, Lennart and Toresson, Håkan and Ruscher, Karsten and Wieloch, Tadeusz},
  issn         = {1872-6240},
  language     = {eng},
  pages        = {92--100},
  publisher    = {Elsevier},
  series       = {Brain Research1966-01-01+01:00},
  title        = {Rho kinase inhibition protects CA1 cells in organotypic hippocampal slices during in vitro ischemia.},
  url          = {http://dx.doi.org/10.1016/j.brainres.2009.11.087},
  volume       = {1316},
  year         = {2010},
}