scholarly journals Endostatin/Collagen XVIII Is Increased in Cerebrospinal Fluid after Severe Traumatic Brain Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hao Chen ◽  
Li-Xia Xue ◽  
He-Li Cao ◽  
Shi-Wen Chen ◽  
Yan Guo ◽  
...  

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6–8 (P<0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P=0.043) and day 7 (P=0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier:NCT01846546.

2008 ◽  
Vol 28 (9) ◽  
pp. 1523-1529 ◽  
Author(s):  
Ericka L Fink ◽  
Yichen Lai ◽  
Xiaopeng Zhang ◽  
Keri Janesko-Feldman ◽  
P David Adelson ◽  
...  

Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinal fluid (CSF). Cerebrospinal fluid samples from 17 pediatric TBI patients and 15 controls were plated overnight and then incubated with polyclonal antibody against PAR. Histone-1, a PARP substrate, was incubated with active PARP, NAD, and nicked DNA, and served as the standard. Both peak and mean CSF PAR-modified proteins were increased in TBI patients versus controls. Peak CSF PAR-modified protein levels occurred on day 1 and levels remained increased on day 2 after TBI. Increases in peak CSF PAR-modified protein concentrations were independently associated with age and male sex, but not initial Glasgow Coma Scale score, Glasgow outcome score, or mechanism of injury. The increase in PAR-modified proteins in CSF after TBI may be because of increased PARP activation, decreased PAR degradation, or both. As PAR-modified protein concentration correlated with age and male sex, developmental and sex-dependent roles for PARP after TBI are implicated.


2007 ◽  
Vol 208 (2) ◽  
pp. 228-237 ◽  
Author(s):  
C.A. Mueller ◽  
H.J. Schluesener ◽  
U. Fauser ◽  
S. Conrad ◽  
J.M. Schwab

2011 ◽  
Vol 114 (5) ◽  
pp. 1471-1478 ◽  
Author(s):  
Arash Farahvar ◽  
Linda M. Gerber ◽  
Ya-Lin Chiu ◽  
Roger Härtl ◽  
Matteus Froelich ◽  
...  

Object The normalization of increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) is assumed to limit secondary brain injury and improve outcome. Despite evidence-based recommendations for monitoring and treatment of elevated ICP, there are few studies that show an association between response to ICP-directed therapeutic regimens and adjusted mortality rate. This study utilizes a large prospective database to examine the effect of response to ICP-lowering therapy on risk of death within the first 2 weeks of injury in patients who sustained TBI and are older than 16 years. Methods The current study is based on 1426 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) of whom 388 were treated for elevated ICP (> 25 mm Hg) between 2000 and 2008 at 22 trauma centers enrolled in a New York State quality improvement program. This prospectively collected database also contains information including age, admission GCS score, pupillary status, CT scanning parameters, and hypotension, which are all known early prognostic indicators of death. Treatment of elevated ICP consisted of administration of mannitol, hypertonic saline, barbiturates, and/or drainage of CSF or decompressive craniectomy. The factors predicting ICP response to treatment and predicting death at 2 weeks were evaluated using logistic regression analyses. Results Increasing age and fewer hours of elevated ICP on Day 1 were found to be significant predictors (p = 0.001 and 0.0003, respectively) of a positive response to treatment. Response to ICP-lowering therapy (p = 0.03), younger age (p < 0.0001), fewer hours of elevated ICP (p < 0.0001), and absence of arterial hypotension on Day 1 (p = 0.001) significantly predicted reduced risk of death. Conclusions Patients who responded to ICP-lowering treatment had a 64% lower risk of death at 2 weeks than those who did not respond after adjusting for factors that independently predict risk of death.


Author(s):  
Simone Bohnert ◽  
Christoph Wirth ◽  
Werner Schmitz ◽  
Stefanie Trella ◽  
Camelia-Maria Monoranu ◽  
...  

AbstractThe aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.


2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Yingming Yue ◽  
Chongzhi Shang ◽  
Huajiang Dong ◽  
Kun Meng

Abstract Objective Severe traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Inflammation induced by TBI is complex, individual-specific, and associated with morbidity and mortality. The aim of the present study was to discover the differentially expressed cerebrospinal fluid (CSF) proteins and identify which can improve the clinical outcomes in TBI patients. Methods In the present study, we reported 145 patients with TBI and found the change in patients’ leukocytes in serum and interleukin-1 (IL-1) in CSF, which strongly correlated with the neurological outcome. In terms of results of leukocytes in blood and IL-1 in CSF, we retained the patient’s CSF specimens and conducted a proteomic analysis. Results A total of 119 differentially expressed proteins were detected between samples of TBI and the normal, which were commonly expressed in all samples, indicating the differentially expressed proteins. When the patients’ Glasgow outcome score (GOS) improved, IL-1 was down-regulated, and when the patients’ GCS score deteriorated, IL-1 was up-regulated accompanied with the progression in TBI. Conclusion The differentially expressed proteins in CSF may be the novel therapeutic targets for TBI treatment. The leukocytes in blood samples and the IL-1 in CSF may be two important indicators for predicting the prognosis of TBI patients.


2019 ◽  
Vol 35 (11) ◽  
pp. 1180-1195 ◽  
Author(s):  
Cristina Sánchez Carabias ◽  
Ana María Castaño-León ◽  
B Blanca Navarro ◽  
Irene Panero ◽  
Carla Eiriz ◽  
...  

Extracranial injury is frequently present in patients with traumatic brain injury (TBI). However, no reliable biomarker exists nowadays to evaluate the magnitude and extension of extracranial injury as well as the identification of patients who are at risk of developing secondary injuries. The purpose of this study was to identify new possible peptide biomarkers by mass spectrometry analysis in patients with TBI and ascertain whether the novel biomarker discovered by peptide mass fingerprinting, serum amyloid A1 (SAA1), is capable of reflecting the condition of the patient and both intracranial and extracranial injury extension. Demographic characteristics, clinical data, and serum samples were prospectively collected from 120 patients with TBI (Glasgow Coma Scale [GCS] score 3-15) on admission. Biomarkers were quantified by enzyme-linked immunosorbent assay. Intracranial lesion volume was measured from the semiautomatic segmentation of hematoma on computed tomography (CT) using Analyze software. Functional outcome was evaluated using the Glasgow Outcome Scale (GOS) at hospital discharge and GOS extended scores at 6 months. The SAA1 levels were significantly associated with intracranial (GCS score at admission, lesion load measured with cranial CT, and pupil responsiveness) and extracranial clinical severity (all Abbreviated Injury Scale regions, Injury Severity Score, major extracranial injury, polytrauma, and orthopedic fractures presence), along with systemic secondary insults and functional outcome. SAA1 was is associated with the volume of traumatic intracranial lesions. The SAA1 levels were correlated with astroglial S100β and glial fibrillary acidic protein (GFAP), neuronal neuron-specific enolase (NSE), and axonal total tau (T-tau) and phosphorylated neurofilament heavy chain (pNF-H) injury markers. SAA1 predicts unfavorable outcome and mortality at hospital discharge (area under the curve [AUC] = 0.90, 0.82) and 6 months (AUC = 0.89). SAA1 can be established as a marker for the overall patient condition due to its involvement in the neuroendocrine axis of the systemic response to craniocerebral trauma.


2019 ◽  
Vol 23 (6) ◽  
pp. 670-679
Author(s):  
Krista Greenan ◽  
Sandra L. Taylor ◽  
Daniel Fulkerson ◽  
Kiarash Shahlaie ◽  
Clayton Gerndt ◽  
...  

OBJECTIVEA recent retrospective study of severe traumatic brain injury (TBI) in pediatric patients showed similar outcomes in those with a Glasgow Coma Scale (GCS) score of 3 and those with a score of 4 and reported a favorable long-term outcome in 11.9% of patients. Using decision tree analysis, authors of that study provided criteria to identify patients with a potentially favorable outcome. The authors of the present study sought to validate the previously described decision tree and further inform understanding of the outcomes of children with a GCS score 3 or 4 by using data from multiple institutions and machine learning methods to identify important predictors of outcome.METHODSClinical, radiographic, and outcome data on pediatric TBI patients (age < 18 years) were prospectively collected as part of an institutional TBI registry. Patients with a GCS score of 3 or 4 were selected, and the previously published prediction model was evaluated using this data set. Next, a combined data set that included data from two institutions was used to create a new, more statistically robust model using binomial recursive partitioning to create a decision tree.RESULTSForty-five patients from the institutional TBI registry were included in the present study, as were 67 patients from the previously published data set, for a total of 112 patients in the combined analysis. The previously published prediction model for survival was externally validated and performed only modestly (AUC 0.68, 95% CI 0.47, 0.89). In the combined data set, pupillary response and age were the only predictors retained in the decision tree. Ninety-six percent of patients with bilaterally nonreactive pupils had a poor outcome. If the pupillary response was normal in at least one eye, the outcome subsequently depended on age: 72% of children between 5 months and 6 years old had a favorable outcome, whereas 100% of children younger than 5 months old and 77% of those older than 6 years had poor outcomes. The overall accuracy of the combined prediction model was 90.2% with a sensitivity of 68.4% and specificity of 93.6%.CONCLUSIONSA previously published survival model for severe TBI in children with a low GCS score was externally validated. With a larger data set, however, a simplified and more robust model was developed, and the variables most predictive of outcome were age and pupillary response.


2021 ◽  
Vol 12 (02) ◽  
pp. 368-375
Author(s):  
Mini Jayan ◽  
Dhaval Shukla ◽  
Bhagavatula Indira Devi ◽  
Dhananjaya I. Bhat ◽  
Subhas K. Konar

Abstract Objectives We aimed to develop a prognostic model for the prediction of in-hospital mortality in patients with traumatic brain injury (TBI) admitted to the neurosurgery intensive care unit (ICU) of our institute. Materials and Methods The clinical and computed tomography scan data of consecutive patients admitted after a diagnosis TBI in ICU were reviewed. Construction of the model was done by using all the variables of Corticosteroid Randomization after Significant Head Injury and International Mission on Prognosis and Analysis of Clinical Trials in TBI models. The endpoint was in-hospital mortality. Results A total of 243 patients with TBI were admitted to ICU during the study period. The in-hospital mortality was 15.3%. On multivariate analysis, the Glasgow coma scale (GCS) at admission, hypoxia, hypotension, and obliteration of the third ventricle/basal cisterns were significantly associated with mortality. Patients with hypoxia had eight times, with hypotensions 22 times, and with obliteration of the third ventricle/basal cisterns three times more chance of death. The TBI score was developed as a sum of individual points assigned as follows: GCS score 3 to 4 (+2 points), 5 to 12 (+1), hypoxia (+1), hypotension (+1), and obliteration third ventricle/basal cistern (+1). The mortality was 0% for a score of “0” and 85% for a score of “4.” Conclusion The outcome of patients treated in ICU was based on common admission variables. A simple clinical grading score allows risk stratification of patients with TBI admitted in ICU.


Author(s):  
Shrikant Govindrao Palekar ◽  
Manish Jaiswal ◽  
Mandar Patil ◽  
Vijay Malpathak

Abstract Background Clinicians treating patients with head injury often take decisions based on their assessment of prognosis. Assessment of prognosis could help communication with a patient and the family. One of the most widely used clinical tools for such prediction is the Glasgow coma scale (GCS); however, the tool has a limitation with regard to its use in patients who are under sedation, are intubated, or under the influence of alcohol or psychoactive drugs. CT scan findings such as status of basal cistern, midline shift, associated traumatic subarachnoid hemorrhage (SAH), and intraventricular hemorrhage are useful indicators in predicting outcome and also considered as valid options for prognostication of the patients with traumatic brain injury (TBI), especially in emergency setting. Materials and Methods 108 patients of head injury were assessed at admission with clinical examination, history, and CT scan of brain. CT findings were classified according to type of lesion and midline shift correlated to GCS score at admission. All the subjects in this study were managed with an identical treatment protocol. Outcome of these patients were assessed on GCS score at discharge. Result Among patients with severe GCS, 51% had midline shift. The degree of midline shift in CT head was a statistically significant determinant of outcome (p = 0.023). Seventeen out of 48 patients (35.4%) with midline shift had poor outcome as compared with 8 out of 60 patients (13.3%) with no midline shift. Conclusion In patients with TBI, the degree of midline shift on CT scan was significantly related to the severity of head injury and resulted in poor clinical outcome.


2021 ◽  
Vol 6 (1) ◽  
pp. e000717
Author(s):  
Panu Teeratakulpisarn ◽  
Phati Angkasith ◽  
Thanakorn Wannakul ◽  
Parichat Tanmit ◽  
Supatcha Prasertcharoensuk ◽  
...  

BackgroundAlthough there are eight factors known to indicate a high risk of intracranial hemorrhage (ICH) in mild traumatic brain injury (TBI), identification of the strongest of these factors may optimize the utility of brain CT in clinical practice. This study aimed to evaluate the predictors of ICH based on baseline characteristics/mode of injury, indications for brain CT, and a combination of both to determine the strongest indicator.MethodsThis was a descriptive, retrospective, analytical study. The inclusion criteria were diagnosis of mild TBI, high risk of ICH, and having undergone a CT scan of the brain. The outcome of the study was any type of ICH. Stepwise logistic regression analysis was used to find the strongest predictors according to three models: (1) injury pattern and baseline characteristics, (2) indications for CT scan of the brain, and (3) a combination of models 1 and 2.ResultsThere were 100 patients determined to be at risk of ICH based on indications for CT of the brain in patients with acute head injury. Of these, 24 (24.00%) had ICH. Model 1 found that injury due to motor vehicle crash was a significant predictor of ICH, with an adjusted OR (95% CI) of 11.53 (3.05 to 43.58). Models 2 and 3 showed Glasgow Coma Scale (GCS) score of 13 to 14 after 2 hours of observation and open skull or base of skull fracture to be independent predictors, with adjusted OR (95% CI) of 11.77 (1.32 to 104.96) and 5.88 (1.08 to 31.99) according to model 2.DiscussionOpen skull or base of skull fracture and GCS score of 13 to 14 after 2 hours of observation were the two strongest predictors of ICH in mild TBI.Level of evidenceIII.


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