Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats

Şahi̇n, Soner; Alkan, Tülin; Temel, Sehime G; Türeyen, Kudret; Tolunay, Şahsine; Korfalı, Ender

doi:10.1016/j.jocn.2009.05.016

Cited by 32 publications

(31 citation statements)

References 31 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that citicoline does not have neuroprotective effects after pilocarpine-induced seizure and that it can even aggravate neuronal degeneration at increased doses. The present results are quite divergent from previous ischemia and traumatic brain injury studies Sahin et al, 2010;Schabitz et al, 1996). The reason why citicoline showed adverse effects in seizure-induced neuronal death is not clear.…”

Section: Discussioncontrasting

confidence: 99%

“…Citicoline (CDP-choline; cytidine 5 0 -diphosphocholine), a naturally occurring endogenous compound, is an important intermediate in the biosynthesis of cell membrane phospholipids (Kennedy and Weiss, 1956). The ability of citicoline to reverse or prevent neuronal injury has been previously tested in animal models of cerebral ischemia Sahin et al, 2010;Schabitz et al, 1996). Citicoline improved the outcome in a randomized, double-blind, placebo-controlled, multicenter clinical Phase III trial (International Citicoline Trial on Acute Stroke [ICTUS]), but provided inconclusive results in recent clinical trials (Davalos et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytidine 5′-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death

et al. 2015

View full text Add to dashboard Cite

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytidine 5′-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death

et al. 2015

View full text Add to dashboard Cite

“…Citicoline acts at several levels of the ischemic cascade in acute ischemic stroke including increase of phosphatidylcholine and sphingomyelin membrane content [32], reduction of glutamate levels [33], inhibition of free-fatty acid release [34], inhibition of apoptosis proteins expression [35], and modifying other antiapoptotic molecules [36]. Apart from these neuroprotective effects, citicoline also possesses a substantial neuroregenerative potential that may explain better its beneficial effects in post-stroke cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment

et al. 2013

View full text Add to dashboard Cite

Background: Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment after stroke. We assessed the safety of long-term administration and its possible efficacy of citicoline in preventing poststroke cognitive decline in patients with first-ever ischemic stroke. Methods: Open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a qualifying stroke and randomized by age, gender, education and stroke type into parallel arms of citicoline (1 g/day) for 12 months vs. no citicoline (control group). Medical management was similar otherwise. All patients underwent neuropsychological evaluation at 1 month, 6 months and 1 year after stroke. Tests results were combined to give indexes of 6 neurocognitive domains: attention and executive function, memory, language, spatial perception, motor speed and temporal orientation. Using adjusted logistic regression models we determined the association between citicoline treatment and cognitive decline for each neurocognitive domain at 6 and 12 months. Results: We recruited 347 subjects (mean age 67.2 years, 186 male (56.6%), mean education 5.7 years); 172 (49.6%) received citicoline for 12 months (no significant differences from controls n = 175). Demographic data, risk factors, initial stroke severity (NIHSS), clinical and etiological classification were similar in both groups. Only 37 subjects (10.7%) discontinued treatment (10.5% citicoline vs. 10.9% control) at 6 months; 30 (8.6%) due to death (16 (9.3%) citicoline vs. 14 (8.0%) control, p = 0.740), 7 lost to follow-up or incorrect treatment, and 4 (2.3%) had adverse events from citicoline without discontinuation. 199 patients underwent neuropsychological evaluation at 1 year. Cognitive functions improved 6 and 12 months after stroke in the entire group but in comparison with controls, citicoline-treated patients showed better outcome in attention-executive functions (OR 1.721, 95% CI 1.065–2.781, p = 0.027 at 6 months; OR 2.379, 95% CI 1.269–4.462, p = 0.007 at 12 months) and temporal orientation (OR 1.780, 95% CI 1.020–3.104, p = 0.042 at 6 months; OR 2.155, 95% CI 1.017–4.566, p = 0.045 at 12 months) during the follow-up. Moreover, citicoline group showed a better functional outcome (modified Rankin scale ≤2) at 12 months (57.3 vs. 48.7%) without statistically significant differences (p = 0.186). Conclusions: Citicoline treatment for 12 months in patients with first-ever ischemic stroke is safe and probably effective in improving poststroke cognitive decline. Citicoline appears to be a promising agent to improve recovery after stroke. Large clinical trials are needed to confirm the net benefit of this therapeutic approach.

show abstract

“…Bcl-2, caspases 3 and 9 as well as Bax proteins were immunohistochemistry tested, showing that the use of citicoline with hypothermia is more effective than citicoline or hypothermia used alone. A decrease in cerebral injury was observed and apparently, the tissue protection is due to the suppression of apoptotic processes (Sahin et al, 2010).…”

Section: Hypothermia and Citicolinementioning

confidence: 98%

Hypothermia as an Alternative for the Management of Cerebral Ischemia

Nares-López¹,

González-Rivera²,

Chánez‐Cárdenas³

2012

Advances in the Treatment of Ischemic Stroke

View full text Add to dashboard Cite

Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats

Cited by 32 publications

References 31 publications

Cytidine 5′-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death

Cytidine 5′-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death

Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment

Hypothermia as an Alternative for the Management of Cerebral Ischemia

Contact Info

Product

Resources

About