Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2005 Jan;30(1):15-23.
doi: 10.1007/s11064-004-9681-8.

Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders

Rao Muralikrishna Adibhatla  1 , J F Hatcher
Affiliations
Review

Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders

Rao Muralikrishna Adibhatla et al. Neurochem Res. 2005 Jan.

Abstract

Brain phosphatidylcholine (PC) levels are regulated by a balance between synthesis and hydrolysis. Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1alpha/beta) activate phospholipase A(2) (PLA(2)) and PC-phospholipase C (PC-PLC) to hydrolyze PC. PC hydrolysis by PLA(2) 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 PLA(2) stimulation and loss of CCT activity. TNF-alpha also stimulates proteolysis of CCT. TNF-alpha and IL-1beta are induced in brain ischemia and may disrupt PC homeostasis by increasing its hydrolysis (increase PLA(2) and PC-PLC activities) and inhibiting its synthesis (decrease CCT activity). The beneficial effects of CDP-choline may result by counteracting TNF-alpha 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
CDP-choline: (A) possible neuroprotective pathways based on the published reports, (B) effects mediated by attenuating PLA2 stimulation (based on authors’ work). ↑ indicates increase; ↓ indicates decrease.
Fig. 2
Fig. 2
TNF-α, IL-1β, CDP-choline and PC homeostasis. (A) Potential pathways of CCT inhibition mediated by TNF-α. TNF-α and IL-1β are induced after brain ischemia (74, 77, 92) and stimulate PLA2 (78) and releases lyso-PC. TNF-α can inhibit CCT activity by two pathways: (1) proteolysis of CCT (93), and/ or (2) inhibition by lyso-PC (91). (B) TNF-α and IL-1β may be responsible for the loss of PC through modulation of PLA2 (78), PC-PLC (80) and CCT (84, 93) following transient cerebral ischemia. Hypothesis: CDP-choline may counteract the TNF-α/IL-1β mediated disruption of PC homeostasis by attenuating PLA2 activation and increasing CCT activity (Fig. 1B). ↑ indicates increase; ↓ indicates decrease. PLAP, PLA2 activating protein.
See this image and copyright information in PMC

References

    1. Fisher M, Brott TG. Emerging therapies for acute ischemic stroke: New therapies on trial. Stroke. 2003;34:359–361. - PubMed
    1. Siao CJ, Fernandez SR, Tsirka SE. Cell type-specific roles for tissue plasminogen activator released by neurons or microglia after excitotoxic injury. J Neurosci. 2003;23:3234–3242. - PMC - PubMed
    1. Secades JJ. CDP-choline: Update and review of its pharmacology and clinical use. Methods Find Exp Clin Pharmacol. 2002;24(Supp B):1–53.
    1. Adibhatla RM, Hatcher JF, Dempsey RJ. Cytidine-5′-diphosphocholine (CDP-choline) affects CTP:phosphocholine cytidylyltransferase and lyso-phosphatidylcholine after transient brain ischemia. J Neurosci Res. 2004;76:390–396. - PubMed
    1. Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: Neuroprotective mechanisms in cerebral ischemia. J Neurochem. 2002;80:12–23. - PubMed

Publication types

MeSH terms

Substances