title: Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders.
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.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792-3232, USA. adibhatl@neurosurg.wisc.edu
authors.forename: Rao Muralikrishna
authors.initials: RM
authors.lastname: Adibhatla
authors.forename: J F
authors.initials: JF
authors.lastname: Hatcher
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D003566:Cytidine Diphosphate Choline