期刊
BRAIN RESEARCH
卷 1316, 期 -, 页码 92-100出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2009.11.087
关键词
Apoptosis; Cell death; Cytoskeleton; Ischemia; Latrunculin; Spine
资金
- Swedish Research Council [8644]
- European Stroke Network [201024]
- The Pia Stahls Foundation
- Swedish Brain Fund
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 M, 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 M. 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. (C) 2009 Published by Elsevier B.V.
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