Deficits in ERK and CREB activation in the hippocampus after traumatic brain injury

Coleen M. Atkins, M. Cristina Falo, Ofelia F. Alonso, Helen M. Bramlett, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Traumatic brain injury (TBI) activates several protein kinase signaling pathways in the hippocampus that are critical for hippocampal-dependent memory formation. In particular, extracellular signal-regulated kinase (ERK), a protein kinase activated during and necessary for hippocampal-dependent learning, is transiently activated after TBI. However, TBI patients experience hippocampal-dependent cognitive deficits that occur for several months to years after the initial injury. Although basal activation levels of ERK return to sham levels within hours after TBI, we hypothesized that activation of ERK may be impaired after TBI. Adult male Sprague-Dawley rats received either sham surgery or moderate parasagittal fluid-percussion brain injury. At 2, 8, or 12 weeks after surgery, the ipsilateral hippocampi of sham surgery and TBI animals were sectioned into transverse slices. After 2 h of recovery in oxygenated artificial cerebrospinal fluid, the hippocampal slices were stimulated with glutamate or KCl depolarization, then analyzed by western blotting for phosphorylated, activated ERK and one of its downstream effectors, the transcription factor cAMP response element-binding protein (CREB). We found that activation of ERK (p < 0.05) and CREB (p < 0.05) after 30 s of glutamate stimulation or KCl depolarization was decreased in hippocampal slices from animals at 2, 8, or 12 weeks after TBI as compared to sham animals. Basal levels of phosphorylated or total ERK were not significantly altered at 2, 8, or 12 weeks after TBI, although basal levels of phosphorylated CREB were decreased 12 weeks post-trauma. These results suggest that TBI results in chronic signaling deficits through the ERK-CREB pathway in the hippocampus.

Original languageEnglish (US)
Pages (from-to)52-56
Number of pages5
JournalNeuroscience Letters
Issue number2
StatePublished - Aug 7 2009


  • CREB
  • ERK
  • Hippocampus
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)


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