Numerous animal experiments and clinical studies have confirmed that citicoline has a neuroprotective effect in the first few hours of cerebral ischemia, and it has the effect of enhancing neuroplasticity and neurorestoration in the subacute phase (days to weeks). These effects are mainly achieved through the following mechanisms: repairing neuronal cell membranes by increasing phosphatidylcholine; stabilizing the neurotransmitter system by increasing the synthesis of acetylcholine and catecholamines; reducing the accumulation of free fatty acid (FFA) in ischemic brain tissue ; Promote energy metabolism in brain tissue.
Mechanism of action of citicoline
1. Neuron cell membrane repair
Brain tissue preferentially utilizes choline to synthesize acetylcholine, which limits the amount of choline available for phosphatidylcholine synthesis. When acetylcholine demand increases or choline reserves decrease, phospholipids in neuronal cell membranes are metabolized to provide the necessary choline. Exogenous administration of citicoline can promote rapid repair of damaged cell membranes and mitochondrial membranes, maintain the integrity of neuron cell membrane structure and function, and down-regulate phospholipase to prevent apoptotic and necrotic cell death. During the subacute phase of stroke, there is a great demand for phospholipid synthesis to support neurogenesis, axonal sprouting, and synaptogenesis. Exogenous administration of citicoline can accelerate phospholipid synthesis and neuronal repair. Animals treated with citicoline during the subacute phase of stroke had better recovery of motor function. Compared with the normal saline control group, rats treated with permanent middle cerebral artery occlusion for 24 h and continued for 28 days with citicoline can improve neural function and enhance the complexity of dendrites and increase the density of spines, suggesting that citicoline Alkaline treatment improves neuronal plasticity and promotes functional recovery in undamaged and functionally connected brain regions.
2. Neurotransmitter Production
Acetylcholine is a neurotransmitter that mediates learning, memory, and a variety of other neurological functions. Cholinergic pathway impairment and reduced acetylcholine release is an important contributor to cognitive impairment after stroke. Citicoline acts as a choline donor in the biosynthesis of acetylcholine. Animal studies of stroke models have shown that administration of citicoline can increase the release of acetylcholine from cholinergic nerve endings and improve the attention, learning and memory functions of animals. Dopamine is a neurotransmitter involved in movement, attention, and a variety of other functions. Citicoline increases dopamine synthesis and may inhibit dopamine reuptake in nerve terminals by promoting tyrosine hydroxylase activity. In addition, animal experiments also found that citicoline can increase the release of norepinephrine in rat cortex and hypothalamus.
3. Reduce FFA accumulation
In ischemic neurons, cellular energy impairment and ATP depletion lead to breakdown of membrane phosphatidylcholine to FFA. FFA can mediate additional tissue damage. FFA is metabolized to toxic oxidative metabolites and free radicals, which also uncouple mitochondrial oxidative phosphorylation. Experimental studies have confirmed that exogenous administration of citicoline can stimulate phosphatidylcholine synthesis and reduce FFA release. In addition, citicoline stabilizes lipid rafts carrying glutamate transporter proteins, thereby promoting the clearance of excitotoxic glutamate from the synaptic cleft.
4. Promote brain tissue energy metabolism
Citicoline has a protective effect on brain cell membrane ATPase and enzymes required for energy metabolism, especially succinate dehydrogenase and citrate synthetase, and also has a protective effect on protein and nucleic acid metabolism, and can increase the concentration of RNA in specific brain regions. Biosynthesis. The glucose uptake rate in the cerebral cortex of rats with global cerebral ischemia was significantly reduced, and citicoline could significantly inhibit this decrease, suggesting that it can improve the energy metabolism of brain tissue under ischemic conditions. Experimental focal ischemia-reperfusion studies also show that citicoline can improve the energy metabolism rate under hypoxic conditions, and large doses of citicoline can significantly improve the neurological function of ischemic animals. This effect is similar to that of citicoline Alkali improves brain tissue metabolism and participates in brain cell membrane phospholipid synthesis.
*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.