C-Jun N-terminal kinase pathway activation in human and experimental cerebral contusion

Fabrizio Ortolano, Alessio Colombo, Elisa Roncati Zanier, Allessandra Sclip, Luca Longhi, Carlo Perego, Nino Stocchetti, Tiziana Borsello, Maria Grazia De Simoni

Research output: Contribution to journalArticlepeer-review


The c-Jun N-terminal kinase (JNK) pathway is involved in cell stress and apoptosis. We tested the hypothesis that this pathway plays a role in traumatic brain injury (TBI) by assessing JNK activation in human brain tissues and in brains of mice subjected to controlled cortical impact brain injury. We also assessed the effects of specific inhibition of the JNK pathway by the cell-permeable JNK inhibitor peptide, D-JNKI1, on neurobehavioral function and posttraumatic cellloss in mice. The inhibitor was administered intraperitoneally 10minutes after injury. The JNK pathway showed robust activation both in human contusion specimens and in injured cortex and hippocampi of TBI-injured mice, 1, 4, and 48 hours after injury. D-JNKI1 treatment significantly improved motor performance at 48 hours and 7days after injury and reduced the contusion volume compared withsaline treatment; the numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were significantly decreased in the hippocampi of injured mice 48 hours after treatment. Thus, because the JNK pathway is activated after human and experimental TBI and the inhibitor peptide D-JNKI1 affords significant neuroprotection and amelioration of neurobehavioral deficits after experimental TBI, therapeutic targeting of the JNK activation pathway may hold promise for future clinical applications.

Original languageEnglish
Pages (from-to)964-971
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Issue number9
Publication statusPublished - Sep 1 2009


  • Brain contusion
  • C-Jun N-terminal kinase pathway
  • D-JNKI1
  • Neuroprotection, Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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