The clinical effect of citicoline sodium combined with Shenxiong glucose in the treatment of senile hypertensive cerebral infarction in the elders / 中国医师杂志

Objective To investigate the clinical therapeutic effect of citicoline sodium combined with Shenxiong glucose in the treatment of senile hypertensive cerebral infarction in the elders.Methods 80 elderly patients with senile hypertensive cerebral infarctiontreated in our hospital were selected and randomly divided into the single treatment group and the combination treatment group,40 cases in each group.Both groups received the routine treatment.The single treatment group additionally received Shenxiong glucose injection (100 ml/d),while patients in the combination treatment group additionally received Shenqiong glucose injection combined with citicoline sodium intravenous infusion therapy (0.5 g/d),both groups were treated for 2 weeks.The levels of serum inflammatory factors,the neurological deficit score,the cognitive function score were compared and analyzed before and after treatment between two groups.Results After systemic treatment,the blood pressure and blood lipid levels of two groups were significantly improved,but there was no significant difference between the two groups (P ＞ 0.05);The serum levels of interleukin (IL)-6,IL-8 and tumor necrosis factor-α (TNF-α) of the combination treatment group improved more significantly (P ≤0.05).After treatment,the oxidative stress indexes were significantly improved in the two groups (P ≤ 0.05).The content of malondialdehyde (MDA) was decreased,while the superoxide dismutase (SOD) activity and nitric oxide (NO) content were increased significantly (P ≤ 0.05);and the improvement degree in the combination treatment group was better than in the single treatment group (P ≤0.05).The degree of improvement in the Modified Edinburgh-Scandinavia Stroke Scale (MESSS) and Hasegawa Dementia Scale (HDS) scores of the combination treatment group was more significant than those in the single treatment group (P ≤ 0.05).The total effective rate of the combination treatment group was 92.5％,which was significantly higher than that of the single group (75.0％),with statistically significant difference (P ≤ 0.05).No obvious adverse reactions happened in two groups during treatment.Conclusions Combination of citicoline sodium and shenxiang glucose on the basis of routine treatment can significantly reduce oxidative stress and inflammation levels,promote the recovery of neurological and cognitive functions,and improve the clinical efficacy and safety.It is worth popularizing and applying in the clinical treatment of senile hypertensive cerebral infarction.

Effect of Recombinant Human Growth Hormone Add on Therapy on Acute Stroke Outcome

Recombinant human growth hormone (rhGH) administration stimulate the secretion of the brain insulin-like growth factor-1 (IGF-1) concentration and IGF-1 is a pleiotropic neurotropic peptide to exert beneficial effect for the injured brain tissues. Citicoline (cytidine-59-diphosphocholine; CDP-choline) is well known to improve neurological outcome in acute stroke. This study aimed to evaluate whether rhGH can potentiate citicoline effect on functional recovery in acute stroke patient. Thirty patients were enrolled. Ten patients were treated with rhGH subcutaneous injection for 6 months on top of citicoline for 6 weeks (GH6 group), and 10 patients for 3 months (GH3 group) with 6 weeks of citicoline treatment as well, and final 10 patients only with citicoline (control group). Functional outcome was determined by Korean modified Barthel Index (K-MBI) and modified Rankin Scale (mRS) at baseline and 6 months after treatment. Seven and 4 patients withdrew from GH6 and GH3 group, respectively. Final 3 patients in GH6 group, 6 patients in GH3 group and 10 patients in control group were analyzed. The K-MBI, and mRS scores from all 3 groups increased in 6 months compared to baseline in intra-group comparison. In inter-group comparison, however, GH6 but not GH3 showed statistically significant improvement compared to control. Administration of rhGH for 6 months on top of 6-week citicoline treatment resulted in further improvement in K-MBI and mRS in acute stroke patients. Further studies in increasing injection dose or injection period is needed.

Effect of citicoline on mild cognitive impairment in patients with middle cerebral artery stenosis / 中华老年心脑血管病杂志

Objective To study the effect of citicoline on mild cognitive impairment MCI) in pa tients with middle cerebral artery stenosis (MCAS).Methods Eighty-six MCAS patients with MCI were divided into citicoline group (n=44) and control group (n=42).The patients in citicoline group were treated with citicoline (0.2 g,3 times a day) for 6 months on the basis of conventional treatment.Cerebrovascular reserve,PI,BHI and Vm between the two groups were compared by transcranial Doppler ultrasonography after treatment.MCI between the two groups was assessed according to the MoCA after treatment.Results The rate of cerebrovascular reserve,PI,BHI and Vm were significantly higher in citicoline group than in control group (13.59％± 1.16％ vs 7.61％±1.12％,P＜0.01;0.51±0.16 vs 0.58±0.12,P＜0.05;1.36±0.08 vs 0.74±0.11,P＜ 0.01;32.63％ ±2.32％ vs 16.92％ ± 1.68％,P＜0.05).The total MoCA score,attention,language,visuospatial and executive function,abstract,naming,orientation and memory were significantly higher in citicoline group than in control group (P＜0.01).Conclusion Early citicoline treatment can improve cerebrovascular reserve and alleviate MCI in MCAS patients.

Early application of citicoline in the treatment of acute stroke: A meta-analysis of randomized controlled trials / 华中科技大学学报（医学）（英德文版）

This study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by meta-analysis. Randomized controlled trials published until May 2015 were electronically searched in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, and China Biology Medicine disc. Two reviewers independently screened the articles and extracted the data based on the inclusion and exclusion criteria. The quality of included articles was evaluated by using Revman5.0, and meta-analysis was performed. The results showed that 1027 articles were obtained in initial retrieval, and finally 7 articles, involving a total of 4039 cases, were included for analysis. The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. The overall rate of adverse events in citicoline group was not significantly different from that in control group (P=0.30). The quality of included articles reached moderate-low level. In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.

Therapeutic effect of citicoline in vascular cognitive impairment / 国际脑血管病杂志

Vascular cognitive impairment refers to all cognitive impairment syndromes associated with vascular diseases,including severe cognitive impairment from mild cognitive impairment to vascular dementia.Citicoline is a necessary intermediate of the phosphatidylcholine biosynthesis,an important component of the neuronal membranes.Experimental studies have shown that citicoline has neuroprotective and neurorepair effects in cerebral ischemia.Clinical studies have shown that citicoline may improve cognitive function in patients with vascular cognitive impairment.

Neuroprotective effect of citicoline on ischemic stroke / 国际脑血管病杂志

Recent experimental ischemic stroke studies have shown that citicoline can not only have neuroprotective effect,but also play the effect of nerve repair by increasing the number of endothelial progenitor cells in peripheral blood,promoting angiogenesis and neurogenesis,and enhancing neuronal plasticity.So far,although the multicenter randomized placebo controlled trials with the largest sample sizethe International Citicoline Trial on Acute Stroke (ICTAS) has obtained a neutral result,the subgroup analyses have shown that citicoline treatment is more effective than placebo of not receiving rtPA thrombolytic therapy,and does not have obvious adverse reaction.Therefore,its application in patients with acute ischemic stroke is reasonable,particularly in those not receiving thrombolytic therapy.

Visual evoked potentials (VEP) and visual acuity improvement after cytidine 52 -diphosphocholine (CDP-Choline) therapy in amblyopic patient / Melhora do potencial evocado visual (PEV) e da acuidade visual em paciente amblíope tratado com citidina difosfato colina

Citicoline may be used in many neurological disorders. Combined treatment of citicoline with patching in amblyopia has previously been researched. The purpose of this paper is to illustrate the effect of citicoline in non-patching amblyopic patient. A 11-year-old amblyopic boy underwent complete ophthalmological examinations, including VEP with flash and pattern stimulus. Two averages of 100 sweep were performed for flash stimulus. Pattern reversal stimulus obtained with high contrast was performed with 60', 30' and 15' checks stimuli. The VEP was repeated 90 days later after a therapy with citicoline and vitamin and the results compared with the responses of the previous recording session. The visual acuity (VA) was 0,7 in the RE and 1,0 in the LE. The VEP pattern amplitude was normal in both eyes. Delayed in latency was detected for all spatial frequency stimulus (SFS) in the RE. Delay in latency was detected only for high SFS in the LE. After the treatment, the VA was 1,0 in both eyes. The latency was normalized with low SFS on the RE and with high SFS on the LE. The flash VEP was normal before and after the therapy. In conclusion, the citicoline demonstrated that it was effective in the treatment of amblyopic eye without patching. The VA and the VEP latency improvement demonstrated that the citicoline enhance the transmission of the electric impulse from retina to visual cortex. Further research is required to understand the immediate and long-term effect of coline treatment in amblyopic patients.

A citicolina pode ser utilizada em vários problemas neurológicos. O tratamento combinado de citicolina e oclusão na ambliopia já foi previamente relatado. O objetivo deste estudo é ilustrar o efeito da citicolina em paciente amblíope sem o tratamento oclusivo. Um menino de 11 anos de idade foi submetido a um exame oftalmológico completo incluindo PEV do tipo flash e do tipo padrão reverso. Para o PEV tipo flash, foram analisadas duas médias de 100 estímulos cada uma. Para o PEV do tipo padrão reverso, foram utilizados estímulos de alto contraste de 60', 30' e 15'. O PEV foi repetido 90 dias depois do tratamento com citicolina e vitaminas e os resultados comparados com os exames antes do tratamento. A acuidade visual era de 0,7 no olho direito e 1,0 no olho esquerdo. A amplitude do PEV era normal em ambos os olhos. Era presente um aumento da latência a todas as frequências espaciais de estimulação (FEE) no olho direito e somente à alta FEE no olho esquerdo. Após o tratamento, a acuidade visual era de 1,0 em ambos os olhos. A latência se normalizou à baixa FSS no olho direito e à alta FSS no olho esquerdo. O PEV tipo flash era normal antes e depois do tratamento. Em conclusão, a citicolina demonstrou ser eficaz no tratamento de olhos amblíopes sem oclusão. A melhora da acuidade visual e da latência do PEV demonstraram que a citicolina restaura a transmissão elétrica do impulso da retina ao cortex visual. Pesquisas futuras são necessárias para entender o efeito imediato e a longo prazo da citicolina no tratamento de pacientes amblíopes.

Influences of levodopa and cytidine diphosphate choline on the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluR2 in visual cortex of monocular deprivation rats / 中华实验眼科杂志

Background Research demonstrated that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluR2 (AMPA-GluR2) is associated with amblyopia.It has been shown that levodopa and cytidine diphosphate choline can improve visual function of amblyopic children,but the mechanism is unclear.Objective This study was to explore the possible effects of levodopa and cytidine diphosphate choline on amblyopia.Methods Monocular deprivation (MD) animal models were created in 60 2-week-old SD rats by monolateral eyelid suturing and observed for 31 days and reared in natural light together with 15 other matched normal healthy SD rats.The models were randomly divided into the MD group,levodopa group,cytidine diphosphate choline group and normal saline control group,with 15 rats for each group.40 mg/kg of levodopa,80 mg/kg of cytidine diphosphate choline,I ml normal saline were given to the rats,respectively,for 28 consecutive days.Expressions of the AMPA-CluR2 protein and AMPA-CluR2 mRNA in the rat visual cortex were detected by immunohistochemistry,Western blot and real-time fluorescence quantitative PCR.Use of the animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results The expression values of the AMPA-GluR2 protein (AMPA-GluR2/β-actin) and AMPA-GluR2 mRNA (2-△△Ct) were significantly lower in the MD group than those of the normal control group (protein:0.32 ± 0.02 vs.0.64 ± 0.05,t =13.287,P＜0.05 ;mRNA:0.30±0.01 vs.0.84±0.03,t=38.184,P＜0.05).Those in the levodopa group were significantly increased in comparison with the normal saline solution group (protein:0.59 ±0.04 vs.0.33 ±0.03,t =11.628,P＜0.05 ; mRNA:0.71±0.06 vs.0.33 ±0.02,t =13.435,P＜0.05).The expression values of the AMPA-GluR2 protein and AMPA-GluR2 mRNA were significantly increased in the cytidine diphosphate choline group compared with the normal saline solution group (protein:0.52 ± 0.04 vs.0.33 ± 0.03,t =8.497,P ＜ 0.05 ; mRNA:0.48± 0.04 vs.0.33 ± 0.02,t =7.500,P＜0.05).Conclusions AMPA-GluR2 is associated with the plasticity of visual development.Levodopa and cytidine diphosphate choline may improve visual function by down-regulating the expression of AMPA-GluR2 in the visual cortex.

Clinical observation of large dose of cytidine diphosphate choline in cardiopulmonary cerebral resuscitation / 中国医师进修杂志

ObjectiveTo explore the treatment efficacy and feasibility of large dose of cytidine diphosphate choline (CDPC) in cardiopulmonary cerebral resuscitation.MethodsOne hundred and thirtytwo patients with sudden cardiac arrest successfully treated by the cardiopulmonary cerebral resuscitation were divided into treatment group ( 75 patients) and control group (57 patients) by random number tables.Two groups of patients were given adrenaline resuscitation drugs,reducing the intracranial pressure drugs,hypothermia,hormones and other basic treatment.Control group used CDPC 0.25 g with glucoseinjection 300 ml to do intravenous drip (once a day,21 days as a period of treatment),and treatment group added CDPC to 2.00 g.The patients were treated by basic traditional analeptic.The Glasgow coma scale (GCS) was carried out in two groups in admission to hospital and 3,7,14,21 days after treatment,and the changes of lysophosphatidic acid (LPA) and phosphatidic acid (AP) level were monitored.ResultsThe GCS score was significantly higher in treatment group 7,14,21 days after treatment(P ＜ 0.05 or ＜ 0.01 ),but GCS score had no significant difference before and after treatment in control group(P ＞ 0.05).The level of LPA in treatment group was significantly decreased 14 days after treatment [ (2.98 ± 0.28) μmol/L ] and 21 days after treatment[ (1.85 ± 0.21)μmol/L],and had significant difference compared with that admission to hospital [ (3.75 ± 0.22) μ mol/L ] (P ＜ 0.05 or ＜ 0.01 ).In control group,there was no significant difference before and after treatment (P ＞0.05).The level of AP in treatment group 21 days after treatment was significantly decreased compared with that in control group [ ( 3.45 ± 0.23 ) μ mol/L vs.( 5.20 ± 0.21 ) μ mol/L ](P ＜ 0.01).ConclusionLarge dose of CDPC can improve neurological function of cardiopulmonary cerebral resuscitation,which is a safe,effective and easy way to be popularized.

Citicoline:a promising agent for neuroprotection and neurorepair / 国际脑血管病杂志

Citicoline is an essential intermediate in the synthesis of structural phospholipids of cell membranes. Exogenously administered citicoline can promote rapid repair of injured neuronal membrane by increasing the synthesis of phospholipids, stabilize neurotransmitter system by increasing the synthesis of acetylcholine and dopamine, and attenuate free fatty acids mediated additional tissue injury by decreasing free fatty acids accumulation in the ischemic cerebral tissue. The wide therapeutic time window, high bioavailability, good blood-brain barrier penetration, and excellent safety make citicoline an effective agent for neuroprotection and neurorepair. Available evidence showed that citicoline can improve significantly neurological function in patients with acute and subacute ischemic stroke. Moreover, animal and clinical studies indicated that citicoline has a potential to improve outcomes of traumatic brain injury,cognitive impairment, intracerebral hemorrhage, Parkinson disease and glaucoma. Citicoline in combination with thrombolytic agents or other neuroprotective agents should become one of the future research directions. The bioavailability and pharmacokinetics of oral citicoline are similar to those of intravenous citicoline, and oral constitutes a main route of administration for citicoline.

Na+ ,K+ -ATPase and cerebral ischemia / 国际脑血管病杂志

The basic functions of the Na+/K+ -ATPase is to maintain the balance of the Na+/K+ electrochemical gradient. The latter is indispensable for maintaining cell osmotic pressure,regulating cell volume,and maintaining excitable membrane resting potential. The maintenance of the Na+/K+ -ATPase activity plays the important roles in neurotransmitter uptake in neurons and Ca2+ effiux. The decreased Na+/K+ -ATPase activity and dysfunction participate in the process of ischemic brain injury after cerebral ischemia. Ischemic precondi-tioning induces ischemic tolerance by maintaining the Na+/K+ -ATPase activity after ischemia.Cardiotonic steroids and citicoline may play a neuroprotective effect on cerebral ischemia by improving the Na +/K+ -ATPase activity.