Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury

David J. Titus, Atsushi Sakurai, Yuan Kang, Concepcion Furones, Stanislava Jergova, Rosmery Santos, Thomas J. Sick, Coleen M. Atkins

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Traumatic brain injury (TBI) modulates several cell signaling pathways in the hippocampus critical for memory formation. Previous studies have found that the cAMP-protein kinase A signaling pathway is downregulated after TBI and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP. In the present study, we examined the effect of rolipram on TBIinduced cognitive impairments.At2weeks aftermoderatefluid-percussion braininjuryorshamsurgery,adultmale SpragueDawleyrats received vehicle or rolipram (0.03 mg/kg) 30 min before water maze acquisition or cue and contextual fear conditioning. TBI animals treated with rolipram showed a significant improvement in water maze acquisition and retention of both cue and contextual fear conditioning compared with vehicle-treated TBI animals. Cue and contextual fear conditioning significantly increased phosphorylated CREB levels in the hippocampus of sham animals, but not in TBI animals. This deficit inCREB activation during learning was rescued in TBI animals treated with rolipram. Hippocampal long-term potentiation was reduced in TBI animals, and this was also rescued with rolipram treatment. These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after TBI, and this may be mediated through increased CREB activation during learning.

Original languageEnglish (US)
Pages (from-to)5216-5226
Number of pages11
JournalAnnals of internal medicine
Volume158
Issue number6
DOIs
StatePublished - Mar 25 2013

ASJC Scopus subject areas

  • Internal Medicine

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