Phosphodiesterase inhibitors as therapeutics for traumatic brain injury

David J. Titus, Anthony A. Oliva, Nicole M. Wilson, Coleen M Atkins

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Developing therapeutics for traumatic brain injury remains a challenge for all stages of recovery. The pathological features of traumatic brain injury are diverse, and it remains an obstacle to be able to target the wide range of pathologies that vary between traumatic brain injured patients and that evolve during recovery. One promising therapeutic avenue is to target the second messengers cAMP and cGMP with phosphodiesterase inhibitors due to their broad effects within the nervous system. Phosphodiesterase inhibitors have the capability to target different injury mechanisms throughout the time course of recovery after brain injury. Inflammation and neuronal death are early targets of phosphodiesterase inhibitors, and synaptic dysfunction and circuitry remodeling are late potential targets of phosphodiesterase inhibitors. This review will discuss how signaling through cyclic nucleotides contributes to the pathology of traumatic brain injury in the acute and chronic stages of recovery. We will review our current knowledge of the successes and challenges of using phosphodiesterase inhibitors for the treatment of traumatic brain injury and conclude with important considerations in developing phosphodiesterase inhibitors as therapeutics for brain trauma.

Original languageEnglish (US)
Pages (from-to)332-342
Number of pages11
JournalCurrent Pharmaceutical Design
Volume21
Issue number3
StatePublished - Jan 1 2015

Keywords

  • CAMP
  • Cognition
  • CREB
  • Hippocampus
  • Inflammation
  • Long-term potentiation
  • Phosphodiesterase
  • Protein kinase A
  • Rolipram
  • Synaptic plasticity
  • Traumatic brain injury

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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