scholarly journals Quantification of Poly(ADP-Ribose)-Modified Proteins in Cerebrospinal Fluid from Infants and Children after Traumatic Brain Injury

2008 ◽  
Vol 28 (9) ◽  
pp. 1523-1529 ◽  
Author(s):  
Ericka L Fink ◽  
Yichen Lai ◽  
Xiaopeng Zhang ◽  
Keri Janesko-Feldman ◽  
P David Adelson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Parp Inhibitors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Parp Activation ◽  
Protein Levels ◽  
Male Sex ◽  
Modified Proteins ◽  
Pediatric Tbi

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.

scholarly journals Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Indirect Association with Intracranial Pressure

2003 ◽  
Vol 23 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Hülya Bayir ◽  
Patrick M. Kochanek ◽  
Shang-Xi Liu ◽  
Antonio Arroyo ◽  
Anatoly Osipov ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Fold Increase ◽  
Infants And Children ◽  
No Production ◽  
Secondary Damage ◽  
Severe Tbi ◽  
Pediatric Tbi

Nitric oxide (NO) is implicated in both secondary damage and recovery after traumatic brain injury (TBI). Transfer of NO groups to cysteine sulfhydryls on proteins produces S-nitrosothiols (RSNO). S-nitrosothiols may be neuroprotective after TBI by nitrosylation of N-methyl-D-aspartate receptor and caspases. S-nitrosothiols release NO on decomposition for which endogenous reductants (i.e., ascorbate) are essential, and ascorbate is depleted in cerebrospinal fluid (CSF) after pediatric TBI. This study examined the presence and decomposition of RSNO in CSF and the association between CSF RSNO level and physiologic parameters after severe TBI. Cerebrospinal fluid samples (n = 72) were obtained from 18 infants and children on days 1 to 3 after severe TBI (Glasgow Coma Scale score < 8) and 18 controls. Cerebrospinal fluid RSNO levels assessed by fluorometric assay peaked on day 3 versus control (1.42 ± 0.11 μmol/L vs. 0.86 ± 0.04, P < 0.05). S-nitrosoalbumin levels were also higher after TBI (n = 8, 0.99 ± 0.09 μmol/L on day 3 vs. n = 6, 0.42 ± 0.02 in controls, P < 0.05). S-nitrosoalbumin decomposition was decreased after TBI. Multivariate analysis showed an inverse relation between CSF RSNO and intracranial pressure and a direct relation with barbiturate treatment. Using a novel assay, the presence of RSNO and S-nitrosoalbumin in human CSF, an ∼1.7-fold increase after TBI, and an association with low intracranial pressure are reported, supporting a possible neuroprotective role for RSNO. The increase in RSNO may result from increased NO production and/or decreased RSNO decomposition.

scholarly journals A New Technique for Collection of Cerebrospinal Fluid in Rat Pups

2015 ◽  
Vol 9 ◽  
pp. JEN.S26182 ◽  
Author(s):  
Javier Rodríguez-Fanjul ◽  
Cristina Durán Fernández-Feijóo ◽  
Marta Camprubí Camprubí
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Practice ◽  
Brain Injury ◽  
Animal Models ◽  
New Technique ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Levels ◽  
Rat Pups ◽  
S100β Protein ◽  
A New Technique

Background Neuroprotective strategies to prevent or decrease brain injury in hypoxic ischemic newborns are one of the main research lines in neonatology. Animal models have been used to assess the efficiency of new therapeutic strategies. Brain damage biomarkers in cerebrospinal fluid (CSF) are frequently used to evaluate the outcome at the bedside. Despite the importance of this approach in clinical practice, there are many difficulties in using it in small animals. The aim of this paper was to describe a new technique for collecting CSF in rat pups. Furthermore the reference values of S100β protein levels, commonly used in common clinical practice, were analyzed in animals between 7 to 12 days. Methods 42 Wistar rat pups aged 7 to 12 days were used. CSF was obtained by direct puncture of the cisterna magna with a 24-gauge needle. S100β protein levels were determined with enzyme-linked immunosorbent assay (ELISA). Results CSF was successfully obtained in 96% of the cases, with an average amount of 21.28 μl (5–40 μl). Normal values for S100β were described. HI animals presented higher S100β values than controls. Conclusions A simple, reproducible technique for CSF collection in rat pups has been described. This new method will allow study of brain injury biomarkers in newborn hypoxic ischemic animal models.

scholarly journals Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury

2021 ◽  
Author(s):  
Simone Bohnert ◽  
Christoph Wirth ◽  
Werner Schmitz ◽  
Stefanie Trella ◽  
Camelia-Maria Monoranu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Myelin Basic Protein ◽  
Immunohistochemical Staining ◽  
Basic Protein ◽  
Staining Intensity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Staining Reaction ◽  
Surrogate Markers

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.

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 ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Dynamic Change ◽  
Angiogenesis Inhibitor ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Secondary Brain Injury ◽  
Collagen Xviii ◽  
Gcs Score

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.

Adherence to Guidelines for Managing Severe Traumatic Brain Injury in Children

2021 ◽  
Vol 30 (5) ◽  
pp. 402-406
Author(s):  
Hengameh B. Pajer ◽  
Anthony M. Asher ◽  
Dennis Leung ◽  
Randaline R. Barnett ◽  
Benny L. Joyner ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Critical Care ◽  
Brain Injury ◽  
Specific Treatment ◽  
Neuromuscular Blocking ◽  
World Federation ◽  
Optimal Timing ◽  
Pediatric Tbi ◽  
The Impact

Pediatric traumatic brain injury (TBI) protocols vary widely among institutions, despite the existence of published guidelines. This study seeks to identify significant differences in management of pediatric TBI across several institutions. Severe pediatric TBI protocols were collected from major US pediatric hospitals through direct communication with trauma staff. Of 24 institutions identified and contacted, 10 did not respond and 5 did not have a pediatric TBI protocol. Pediatric TBI protocols were successfully collected from 9 institutions. These 9 protocols were separated into treatment tiers analogous to those in the 2019 Society of Critical Care Medicine and World Federation of Pediatric Intensive and Critical Care Societies guidelines, and the intervention variables were identified and compared across the 9 institutions. First-line therapies were similar between institutions, including seizure prophylaxis, maintenance of normoglycemia and normothermia, and avoidance of hypoxia, hyponatremia, and hypotension. However, significant variation across institutions was found regarding timing of cerebrospinal fluid drainage, hyperventilation, and neuromuscular blockade. When included in institutional protocols, most therapies are in line with the 2019 guidelines, except for diversion of cerebrospinal fluid, hyperventilation, maintenance of cerebral perfusion pressure, and use of neuromuscular blocking agents. Although these variations may represent differences in style or preference, the optimal timing of these specific treatment variations should be studied to determine the impact of each protocol on clinical outcomes.

One-year costs of intensive care in pediatric patients with traumatic brain injury

2021 ◽  
Vol 27 (1) ◽  
pp. 79-86
Author(s):  
Era D. Mikkonen ◽  
Markus B. Skrifvars ◽  
Matti Reinikainen ◽  
Stepani Bendel ◽  
Ruut Laitio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Intensive Care ◽  
Brain Injury ◽  
Social Security ◽  
Functional Outcome ◽  
Injury Severity ◽  
Pediatric Population ◽  
Favorable Outcome ◽  
Index Hospitalization ◽  
Pediatric Tbi

OBJECTIVETraumatic brain injury (TBI) is a major cause of death and disability in the pediatric population. The authors assessed 1-year costs of intensive care in pediatric TBI patients.METHODSIn this retrospective multicenter cohort study of four academic ICUs in Finland, the authors used the Finnish Intensive Care Consortium database to identify children aged 0–17 years treated for TBI in ICUs between 2003 and 2013. The authors reviewed all patient health records and head CT scans for admission, treatment, and follow-up data. Patient outcomes included functional outcome (favorable outcome defined as a Glasgow Outcome Scale score of 4–5) and death within 6 months. Costs included those for the index hospitalization, rehabilitation, and social security up to 1 year after injury. To assess costs, the authors calculated the effective cost per favorable outcome (ECPFO).RESULTSIn total, 293 patients were included, of whom 61% had moderate to severe TBI (Glasgow Coma Scale [GCS] score 3–12) and 40% were ≥ 13 years of age. Of all patients, 82% had a favorable outcome and 9% died within 6 months of injury. The mean cost per patient was €48,719 ($54,557) (95% CI €41,326–€56,112). The index hospitalization accounted for 66%, rehabilitation costs for 27%, and social security costs for 7% of total healthcare costs. The ECPFO was €59,727 ($66,884) (95% CI €52,335–€67,120). A higher ECPFO was observed among patients with clinical and treatment-related variables indicative of parenchymal swelling and high intracranial pressure. Lower ECPFO was observed among patients with higher admission GCS scores and those who had epidural hematomas.CONCLUSIONSGreater injury severity increases ECPFO and is associated with higher postdischarge costs in pediatric TBI patients. In this pediatric cohort, over two-thirds of all resources were spent on patients with favorable functional outcome, indicating appropriate resource allocation.

scholarly journals Longitudinal Growth Curve Trajectories of Family Dynamics after Pediatric Traumatic Brain Injury in Mexico

2020 ◽  
Vol 17 (22) ◽  
pp. 8508
Author(s):  
Grace B. McKee ◽  
Laiene Olabarrieta-Landa ◽  
Paula K. Pérez-Delgadillo ◽  
Ricardo Valdivia-Tangarife ◽  
Teresita Villaseñor-Cabrera ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Family Functioning ◽  
Growth Curve ◽  
Family Members ◽  
Family Satisfaction ◽  
Health Concern ◽  
Pediatric Traumatic Brain Injury ◽  
Large Hospital ◽  
Pediatric Tbi

Pediatric traumatic brain injury (TBI) represents a serious public health concern. Family members are often caregivers for children with TBI, which can result in a significant strain on familial relationships. Research is needed to examine aspects of family functioning in the context of recovery post-TBI, especially in Latin America, where cultural norms may reinforce caregiving by family members, but where resources for these caregivers may be scarce. This study examined caregiver-reported family satisfaction, communication, cohesion, and flexibility at three time points in the year post-injury for 46 families of a child with TBI in comparison to healthy control families. Families experiencing pediatric TBI were recruited from a large hospital in Guadalajara, Mexico, while healthy controls were recruited from a local educational center. Results from multilevel growth curve models demonstrated that caregivers of children with a TBI reported significantly worse family functioning than controls at each assessment. Families experiencing pediatric TBI were unable to attain the level of functioning of controls during the time span studied, suggesting that these families are likely to experience long-term disruptions in family functioning. The current study highlights the need for family-level intervention programs to target functioning for families affected by pediatric TBI who are at risk for difficulties within a rehabilitation context.

scholarly journals ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽  
2009 ◽  
Vol 65 (4) ◽  
pp. 702-708 ◽  
Author(s):  
Mark Grossetete ◽  
Jeremy Phelps ◽  
Leopold Arko ◽  
Howard Yonas ◽  
Gary A. Rosenberg
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Blood Brain Barrier ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Brain Barrier ◽  
Western Immunoblot ◽  
Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P &lt; 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

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