The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.
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ABSTRACT: Objective
We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients.Methods
Patients were randomly assigned into two groups (n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days.Results
NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively (p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively (p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively (p = 0.031). NSE serum levels and GCS scores were negatively correlated (r = -0.569, p < 0.001).Conclusion
Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.
SUBMITTER: Mansour NO
PROVIDER: S-EPMC8246481 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSeveral studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.MethodsPubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded.ResultsSixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66-0.80) for unfavorable outcome and 0.76 (95% CI, 0.62-0.90) for mortality.ConclusionsMortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.
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Project description:Background: Experimental evidence has indicated the benefits of intraoperative controlled decompression for the treatment of severe traumatic brain injury (sTBI). Intraoperative rapid decompression (conventional decompression) for the treatment of sTBI may result in intra- and post-operative complications. Controlled decompression may reduce these complications. Previous clinical trials in China have not yielded conclusive results regarding controlled decompression for sTBI. Therefore, we explored whether controlled decompression treatment decreases the rates of complications and improves the outcomes of patients with sTBI. Methods: We performed this randomized, controlled trial at our hospital. Patients with sTBI aged 18-75 years old were randomly (1:1) divided into controlled decompression surgery (n = 124) or rapid decompression surgery groups (n = 124). The primary outcome measures were the Extended Glasgow Outcome Scale (GOS-E) score at 6 months and 30-days all-cause mortality. The secondary outcomes were the incidences of intraoperative brain swelling, post-traumatic cerebral infarction, and delayed hematoma. Results: Compared with the rapid decompression group, the controlled decompression group had reduced 30-days all-cause mortality (18.6 vs. 30.8%, P = 0.035) and improved the 6-months GOS-E scores, and the difference was significant. In addition, the patients in the controlled decompression group had a lower intraoperative brain swelling rate (13.3 vs. 24.3%, P = 0.036), a lower delayed hematoma rate (17.7 vs. 29.0%, P = 0.048) and a relatively lower post-traumatic cerebral infarction rate (15.0 vs. 22.4%, P = 0.127) than those in the rapid decompression group. Conclusions: Our data suggest that controlled decompression surgery significantly improves sTBI outcomes and decreases the rates of sTBI-related complications. However, this was a single-hospital study, and well-designed multicenter randomized controlled trials are needed to evaluate the effects of controlled decompression surgery for the management of patients with sTBI. Clinical Trial Registration: Chinese Clinical Trial Registry; Date: 14/Dec/2013; Number: ChiCTR-TCC-13004002.
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Project description:BackgroundPrognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury.MethodsWe searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses.ResultsWe screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ? 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data.InterpretationIn patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available.
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Project description:In an effort to understand the complexity of genomic responses within selectively vulnerable regions after experimental brain injury, we examined whether single apoptotic neurons from both the CA3 and dentate differed from those in an uninjured brain. The mRNA from individual active caspase 3(+)/terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling [TUNEL(-)] and active caspase 3(+)/TUNEL(+) pyramidal and granule neurons in brain-injured mice were amplified and compared with those from nonlabeled neurons in uninjured brains. Gene analysis revealed that overall expression of mRNAs increased with activation of caspase 3 and decreased to below uninjured levels with TUNEL reactivity. Cell type specificity of the apoptotic response was observed with both regionally distinct expression of mRNAs and differences in those mRNAs that were maximally regulated. Immunohistochemical analysis for two of the most highly differentially expressed genes (prion and Sos2) demonstrated a correlation between the observed differential gene expression after traumatic brain injury and corresponding protein translation.
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Project description:The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability. The loss of BBB integrity by the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) is critical to TBI-induced BBB hyperpermeability, and doxycycline possesses anti-MMP-9 effect. In this study, the effect of doxycycline on BBB hyperpermeability was studied utilizing molecular modeling (using Glide) in silico, cell culture-based models in vitro, and a mouse model of TBI in vivo. Brain microvascular endothelial cell assays of tight junction protein immunofluorescence and barrier permeability were performed. Adult C57BL/6 mice were subjected to sham versus TBI with or without doxycycline treatment and immediate intravital microscopic analysis for evaluating BBB integrity. Postmortem mouse brain tissue was collected to measure MMP-9 enzyme activity. It was found that doxycycline binding to the MMP-9 active sites have binding affinity of -7.07 kcal/mol. Doxycycline treated cell monolayers were protected from microvascular hyperpermeability and retained tight junction integrity (p < 0.05). Doxycycline treatment decreased BBB hyperpermeability following TBI in mice by 25% (p < 0.05). MMP-9 enzyme activity in brain tissue decreased with doxycycline treatment following TBI (p < 0.05). Doxycycline preserves BBB tight junction integrity following TBI via inhibiting MMP-9 activity. When established in human subjects, doxycycline, may provide readily accessible medical treatment after TBI to attenuate secondary injury.
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Project description:Traumatic brain injury (TBI) is a worldwide health concern associated with significant morbidity and mortality. In the United States, severe TBI is managed according to recommendations set forth in 2007 by the Brain Trauma Foundation (BTF), which were based on relatively low quality clinical trials. These guidelines prescribed the use of hypothermia for the management of TBI. Several randomized controlled trials (RCTs) of hypothermia for TBI have since been conducted. Despite this new literature, there is ongoing controversy surrounding the use of hypothermia for the management of severe TBI.We searched the PubMed database for all RCTs of hypothermia for TBI since 2007 with the intent to review the methodology outcomes of these trials. Furthermore, we aimed to develop evidence-based, expert opinions based on these recent studies.We identified 8 RCTs of therapeutic hypothermia published since 2007 that focused on changes in neurologic outcomes or mortality in patients with severe TBI. The majority of these trials did not identify improvement with the use of hypothermia, though there were subgroups of patients that may have benefited from hypothermia. Differences in methodology prevented direct comparison between studies.A growing body of literature disfavors the use of hypothermia for the management of severe TBI. In general, empiric hypothermia for severe TBI should be avoided. However, based on the results of recent trials, there may be some patients, such as those in Asian centers or with focal neurologic injury, who may benefit from hypothermia.
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Project description:PurposeMild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents.MethodsBlood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed.ResultsThe NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68); and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64).ConclusionAn increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury.
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Project description:Study aimed at examining differential expression between single apoptotic neurons from both the CA-3 and dentate and those in an un-injured brain.
2005-11-02 | E-CBIL-4 | biostudies-arrayexpress
Project description:BackgroundPediatric traumatic brain injury (TBI) contributes to impairments in functioning in everyday settings. Evidence suggests that online family problem-solving therapy (FPST) may be effective in reducing adolescent behavioral morbidity. This article examines the efficacy of Counselor-Assisted Problem Solving (CAPS), a form of online FPST in improving long-term functional outcomes of adolescents with TBI relative to Internet resources only.MethodsChildren, aged 12 to 17 years, who were hospitalized in the previous 7 months for TBI were enrolled in a multisite, assessor-blinded randomized controlled trial. Consented participants were randomly assigned to CAPS or an Internet resource comparison (IRC) condition. Outcomes were assessed at baseline and at follow-ups 6, 12, and 18 months postbaseline. The Child and Functional Assessment Scale and the Iowa Family Interaction Rating Scale (IFIRS) served as primary outcomes of child and family functioning respectively.ResultsFor the Child and Functional Assessment Scale total, we found a significant group × time interaction, with less impaired functioning for the CAPS group than for the IRC group at the final follow-up. Parent education moderated the efficacy of CAPS on overall rates of impairment and school/work functioning, with the advantage of CAPS over IRC evident at the final follow-up only for participants with less-educated parents. Neither group differences nor group × time interactions were found for the IFIRS.ConclusionsRelatively brief, online treatment shortly after injury may result in long-term improvements in child functioning, particularly among families of lower socioeconomic status. Clinical implementation of CAPS during the initial months postinjury should be considered.
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