Thrombin-induced ischemic tolerance is prevented by inhibiting c-jun N-terminal kinase

Cristina Granziera, Jonathan Thevenet, Melanie Price, Karine Wiegler, Pierre Magistretti, Jérôme Badaut, Lorenz Hirt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

We have studied ischemic tolerance induced by the serine protease thrombin in two different models of experimental ischemia. In organotypic hippocampal slice cultures, we demonstrate that incubation with low doses of thrombin protects neurons against a subsequent severe oxygen and glucose deprivation. l-JNKI1, a highly specific c-jun N-terminal kinase (JNK) inhibitor, and a second specific JNK inhibitor, SP600125, prevented thrombin preconditioning (TPC). We also show that the exposure to thrombin increases the level of phosphorylated c-jun, the major substrate of JNK. TPC, in vivo, leads to significantly smaller lesion sizes after a 30-min middle cerebral artery occlusion (MCAo), and the preconditioned mice were better off in the three tests used to evaluate functional recovery. In accordance with in vitro results, TPC in vivo was prevented by administration of l-JNKI1, supporting a role for JNK in TPC. These results, from two different TPC models and with two distinct JNK inhibitors, show that JNK is likely to be involved in TPC.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalBrain Research
Volume1148
Issue number1
DOIs
StatePublished - May 7 2007

Keywords

  • Hippocampal slice culture
  • Ischemia
  • Middle cerebral artery occlusion
  • Thrombin
  • Tolerance
  • c-jun N-terminal kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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