Neurochemical Research

, Volume 30, Issue 1, pp 15–23 | Cite as

Cytidine 5′-Diphosphocholine (CDP-Choline) in Stroke and Other CNS Disorders

Article

Abstract

Brain phosphatidylcholine (PC) levels are regulated by a balance between synthesis and hydrolysis. Pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1α/β) activate phospholipase A2 (PLA2) and PC-phospholipase C (PC-PLC) to hydrolyze PC. PC hydrolysis by PLA2 releases free fatty acids including arachidonic acid, and lyso-PC, an inhibitor of CTP-phosphocholine cytidylyltransferase (CCT). Arachidonic acid metabolism by cyclooxygenases/lipoxygenases is a significant source of reactive oxygen species. CDP-choline might increase the PC levels by attenuating PLA2 stimulation and loss of CCT activity. TNF-α also stimulates proteolysis of CCT. TNF-α and IL-1β are induced in brain ischemia and may disrupt PC homeostasis by increasing its hydrolysis (increase PLA2 and PC-PLC activities) and inhibiting its synthesis (decrease CCT activity). The beneficial effects of CDP-choline may result by counteracting TNF-α and/or IL-1 mediated events, integrating cytokine biology and lipid metabolism. Re-evaluation of CDP-choline phase III stroke clinical trial data is encouraging and future trails are warranted. CDP-choline is non-xenobiotic, safe, well tolerated, and can be considered as one of the agents in multi-drug treatment of stroke.

Keywords

Cerebral ischemia citicoline clinical trials interleukin-1β phospholipases phospholipids reactive oxygen species tumor necrosis factor lipidomics 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Rao Muralikrishna Adibhatla
    • 1
    • 2
    • 3
    • 4
  • J. F. Hatcher
    • 1
  1. 1.Department of Neurological SurgeryUniversity of WisconsinMadison
  2. 2.Cardiovascular Research CenterUniversity of WisconsinMadison
  3. 3.Veterans Administration HospitalMadison
  4. 4.Department of Neurological SurgeryClinical Science Center, University of Wisconsin-MadisonMadison

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