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Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury.
J Neurosci. 2013 Mar 20; 33(12):5216-26.JN

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 TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats 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 in CREB 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.

Authors+Show Affiliations

Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23516287

Citation

Titus, David J., et al. "Phosphodiesterase Inhibition Rescues Chronic Cognitive Deficits Induced By Traumatic Brain Injury." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 33, no. 12, 2013, pp. 5216-26.
Titus DJ, Sakurai A, Kang Y, et al. Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury. J Neurosci. 2013;33(12):5216-26.
Titus, D. J., Sakurai, A., Kang, Y., Furones, C., Jergova, S., Santos, R., Sick, T. J., & Atkins, C. M. (2013). Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33(12), 5216-26. https://doi.org/10.1523/JNEUROSCI.5133-12.2013
Titus DJ, et al. Phosphodiesterase Inhibition Rescues Chronic Cognitive Deficits Induced By Traumatic Brain Injury. J Neurosci. 2013 Mar 20;33(12):5216-26. PubMed PMID: 23516287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury. AU - Titus,David J, AU - Sakurai,Atsushi, AU - Kang,Yuan, AU - Furones,Concepcion, AU - Jergova,Stanislava, AU - Santos,Rosmery, AU - Sick,Thomas J, AU - Atkins,Coleen M, PY - 2013/3/22/entrez PY - 2013/3/22/pubmed PY - 2013/5/29/medline SP - 5216 EP - 26 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 33 IS - 12 N2 - 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 TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats 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 in CREB 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. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/23516287/Phosphodiesterase_inhibition_rescues_chronic_cognitive_deficits_induced_by_traumatic_brain_injury_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=23516287 DB - PRIME DP - Unbound Medicine ER -