Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic Brain Injury

Zafonte, Ross; Bagiella, Emilia; Ansel, Beth M.; Novack, Thomas A.; Friedewald, William T.; Hesdorffer, Dale C.; Timmons, Shelly D.; Jallo, Jack; Eisenberg, Howard M.; Hart, Tessa; Ricker, Joseph H.; Diaz‐Arrastia, Ramon; Merchant, Randall E.; Temkin, Nancy; Melton, Sherry M.; Dikmen, Sureyya

doi:10.1001/jama.2012.13256

Cited by 161 publications

(130 citation statements)

References 33 publications

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“…Baseline CT scans, vital signs, medical history, demographics, and injury information were obtained and recorded as described elsewhere. 29 Non-fasting blood samples were collected from COBRIT participants within 24 h of injury and again at 30 and 90 days after injury. Blood was collected into plastic dipotassium ethylenediaminetetraacetic acid (EDTA) tubes, immediately placed on ice, centrifuged (15 min, 2000g, room temperature) and frozen in aliquots within 1 h after collection.…”

Section: Study Populationmentioning

confidence: 99%

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Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Bogoslovsky

Wilson

Yao

et al. 2017

Journal of Neurotrauma

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174

126

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Glial fibrillary acidic protein (GFAP), microtubule-associated protein tau, and amyloid b peptide (Ab42) have been proposed as diagnostic and prognostic biomarkers in traumatic brain injury (TBI). Single molecule array (Simoa) is a novel technology that employs highly sensitive immunoassays for accurate measurements of candidate biomarkers found at low concentration in biological fluids. Our objective was to trace the trajectory of tau, GFAP, and Ab42 levels in plasma from the acute through subacute stages after TBI, compared with controls. Samples from 34 TBI subjects enrolled in the Citicoline Brain Injury Treatment Trial (COBRIT) were studied. Injury severity was assessed by Glasgow Coma Scale (GCS) and admission CT. Glasgow Outcome Scale Extended (GOSE) was assessed 6 months after injury. Plasma was collected within 24 h (Day 0), and 30 and 90 days after the TBI. Plasma collected from 69 healthy volunteers was used for comparison. At every time point, increases were noted in plasma GFAP ( p < 0.0001 for all comparisons), tau ( p < 0.0001, p < 0.0001, and p = 0.0044, at Days 0, 30, and 90, respectively), and Ab42 ( p < 0.001, p < 0.0001, and p = 0.0203, respectively) in TBI cases compared with controls. The levels were maximal at Day 0 for GFAP and tau and at Day 30 for Ab42. Area under curve (AUC) analyses for Day 0 GFAP and tau were excellent for discrimination of complicated mild TBI (cmTBI) from controls (0.936 and 0.901, correspondingly). Discriminant component analysis (DCA) for all three biomarkers at Days 0 and 30 differentiated controls from cmTBI (91.1% and 89.7% correctly classified, at each time point). Duration of post-traumatic amnesia (PTA) correlated weakly with tau levels at 30 days (Spearman's r = 0.40; 95% CI 0.0003-0.60, p = 0.044). The Marshall CT Grade on admission correlated weakly with Day 30 tau levels (Spearman's r = 0.41; 95% CI 0.04-0.68, p = 0.027). Day 30 Ab42 correlated with GOSE (standardized b -0.486, p = 0.042). GFAP, tau and Ab42 were increased up to 90 days after TBI compared with controls. Total tau levels correlated with clinical and radiological variables of TBI severity. Plasma Ab42 correlated with clinical outcome. Combination of all three biomarkers at Days 0 and 30 can be used to differentiate controls from cmTBI populations, and may be useful as biomarkers of TBI in both acute and subacute phases.

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Section: Study Populationmentioning

confidence: 99%

“…There was no benefit from citicoline treatment noted in the COBRIT trial. 29 A subset of the COBRIT TBI participants enrolled at a single site donated blood for future biomarker research, and these well-characterized samples were tested in this study. We hypothesized that:…”

mentioning

confidence: 99%

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Bogoslovsky

Wilson

Yao

et al. 2017

Journal of Neurotrauma

Self Cite

174

126

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“…With the increase of calcium salt deposition during the middle and late stages of osteogenic differentiation, activities of ALP gradually decrease (16). OCN is a common signal molecule that promotes osteogenesis and bone inducing factors (17). OCN is a common signal molecule to promote osteogenesis of bone inducing factors (18).…”

Section: Discussionmentioning

confidence: 99%

Anti‑aging effect of fullerenol on skin aging through derived stem cells in a mouse model

Sui

et al. 2017

Exp Ther Med

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Abstract.Fullerenol is similar to graphite in terms of structure. In the present study, the anti-aging effect of fullerenol on skin through derived stem cells in a mouse model was assessed and the potential mechanism of fullerenol was investigated. The anti-aging effect of fullerenol effectively inhibited the retention rate of transplanted adipose-derived stem cells and increased the thickness of the dermal portion of skin and collagen ratio in mice. The effect of fullerenol on the proliferation of stem cells was observed. Treatment with fullerenol effectively promoted the mRNA expression of Runt-related transcription factor 2, alkaline phosphatase and osteocalcin in a mouse model of skin aging induced by D-galactose. However, fullerenol treatment effectively suppressed the protein expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased forkhead box protein O1 (FoxO1) protein expression in the mice model of skin aging induced by D-galactose. These results demonstrate that the anti-aging effect of fullerenol on skin through derived stem cells may be mediated in mice via the PPAR-γ/FoxO1 signaling pathway.

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“…In addition, the findings on phase-III RCTs for TBI management challenged the former evidence of neuroprotective agent use (i.e., CRASH 2005 for Corticosteroid (4), COR-BIT 2012 for Citicoline (17), SYNAPSE 2014 (18) and ProTECT 2014 (19) for progesterone, and EPO-TBI 2015 for erythropoietin (9)). Despite the current process of phase-I to phase-III (IV) drug evaluation for use in human-beings, it is recommended to skip phase-II trials for TBI related studies.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Meshkini¹,

Meshkini²,

Sadeghi‐Bazargani³

2016

Trauma Mon

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Context: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity; despite the use of neuroprotective agents for TBI management, no evidence-based recommendation for any particular neuroprotective agent with favorable outcomes and less adverse effects has been made in TBI management. Objectives: We aimed to assess the efficacy of erythropoietin (EPO) use for TBI management. Data Sources: This study is part of a review on neuroprotective agents used for traumatic brain injury: A systematic review and meta-analyses was done, based on a wide search strategy incorporating information from Cochrane CENTRAL, MedLine/PubMed, SCOPUS, Thomson Reuters Web of Science, SID.ir, Barekat Foundation, and clinicaltrials.gov databases up to September 06, 2015. Study Selection: The present study limited the retrieved search results only to those using EPO for TBI management. Data Extraction: The retrieved randomized clinical trials (RCTs) were assessed for their quality of reporting according to the consolidated standards of reporting trials (CONSORT) checklist prior to extracting the data for meta-analysis. The meta-analyses in this review was conducted using the extended Glasgow outcome scale (GOS-E) for acute TBI patients, mortalities, and adverse-effects. Results: Four RCTs were retrieved on EPO use for acute TBI, and two of them were kept for the final analysis. The analysis of the enrolled 645 participants in these studies showed insignificant but slightly better outcomes in the placebo group, while a significant reduction in mortality rates among EPO users was observed. Slightly better outcomes in vascular and non-vascular side-effects were also observed in the intervention group. Conclusions: EPO may be considered as effective in reducing TBI mortality and vascular side-effects, while there is no evidence to support any benefits in other outcomes or for the elimination of non-vascular side-effects. Further studies, especially well-designed phase-III dose-controlled trials, are needed for building a stronger body of evidence for recommending the use of EPO for acute TBI.Keywords: Head Injury, Traumatic Brain Injury, Neuroprotective Agent, Erythropoietin, Review ContextTraumatic brain injury (TBI), which is also known as head injury (1-3), is a leading cause of mortality and morbidity (1, 4-6), especially among those of young ages (1).Epidemiological studies have demonstrated the following facts about TBI in the U.S. (1, 4): -There is an incidence rate of 558 cases per 100,000 people each year.-TBI-related disability cases are estimated as rising by 33 new cases per 100,000 people each year.-They cause more than 50,000 deaths each year.-Motor vehicle collisions (MVC) are responsible for 50% of TBI cases.TBI costs more than $48 billion a year, and between 2.5 and 6.5 million Americans alive today have been victims of a TBI-related assault. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities (7).Erythropoietin (EPO) is a glycoprotein hormone of the cy...

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Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic Brain Injury

Abstract: clinicaltrials.gov Identifier: NCT00545662.

Cited by 161 publications

References 33 publications

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Anti‑aging effect of fullerenol on skin aging through derived stem cells in a mouse model

Erythropoietin for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

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