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Citicoline and Docosahexaenoic Acid Following Experimental Brain Ischemia

8/20/2019 12:57:57 PM
ischemiaTransient ischemic attacks (TIAs) cause approximately one in 4 ischemic strokes, leading to cognitive dysfunction and long-term disabilities. Clinical stroke trials suggest that citicoline may offer some neuroprotective benefits, but the ICTUS randomized controlled trial found similar global recovery for citicoline and placebo groups. Exploring combination therapies to synergize with citicoline supplementation is, therefore, a reasonable next step.

Researchers examine citicoline and DHA for cognitive function

As reported in a 2019 publication of the Journal of Pharmacological Sciences, researchers investigated whether citicoline and docosahexaenoic acid (DHA) supplementation would have a synergistic effect on cognitive dysfunction, neuronal cell death, and molecular changes in phospholipids in a mouse model of TIA.
Mice were divided into 6 groups: sham-control, sham-combination (DHA 300 mg/kg + citicoline 40 mg/kg), ischemia-control, ischemia-DHA, ischemia-citicoline, and ischemia-combination. Results showed that the combination of citicoline and DHA improved contextual memory and recognition memory deficits in ischemia-induced mice. Combined citicoline and DHA also prevented neuronal cell death induced by ischemia in the hippocampal region. The supplement combination increased levels of DHA-enriched phosphatidylcholine in the hippocampus, but not to a statistically significant level.

Results suggest citicoline and DHA supplementation beneficial

Mechanisms to explain the neuroprotective effects of citicoline and DHA likely involve their role in supporting the synthesis of phosphatidylcholine. Phosphatidylcholine decreases in the brain following ischemia, releasing free fatty acids that promote inflammation. Citicoline is an essential intermediate in phosphatidylcholine synthesis and stabilizes membrane phospholipids. DHA enriches neuronal cell membranes, is found in phosphatidylcholine and phosphatidylethanolamine, and counteracts the inflammatory effects of other free fatty acids.
Human clinical trials are needed, but this preliminary animal study suggests that combined supplementation with citicoline and DHA may offer neuroprotective effects following transient brain ischemia.
Nakazaki E, Yabuki Y, Izumi H et al. Combined citicoline and docosahexaenoic acid treatment improves cognitive dysfunction following transient brain ischemia. J Pharmacol Sci. 2019; 139: 319-324.