Src kinase inhibition decreases thrombin-induced injury and cell cycle re-entry in striatal neurons

Da Liu, Xi Yuan Cheng, Bradley Ander, Huichun Xu, Ryan R. Davis, Jeffrey Gregg, Frank R Sharp

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease thrombin-induced brain injury. Thrombin injections into adult rat striatum produced focal infarction and motor deficits. The Src kinase inhibitor PP2 decreased thrombin-induced Src activation, infarction in striatum and motor deficits in vivo. Thrombin applied to cultured post-mitotic striatal neurons caused: injury to axons and dendrites; many TUNEL positive neuronal nuclei; and re-entry into the cell cycle as manifested by cyclin D1 expression, induction of several other cell cycle genes and cyclin-dependent kinase 4 activation. PP2 dose-dependently attenuated thrombin-induced injury to the cultured neurons; and attenuated thrombin-induced neuronal cell cycle re-entry. These results are consistent with the hypotheses that Src kinase inhibitors decrease injury produced by ICH by decreasing thrombin activation of Src kinases and, at least in part, by decreasing Src induced cell cycle re-entry.

Original languageEnglish (US)
Pages (from-to)201-211
Number of pages11
JournalNeurobiology of Disease
Volume30
Issue number2
DOIs
StatePublished - May 2008

Keywords

  • Cell cycle
  • Intracerebral hemorrhage
  • Mitogenic signaling
  • Neuronal apoptosis
  • Striatum
  • Thrombin

ASJC Scopus subject areas

  • Neurology

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