Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum*

Fraser, Douglas D.; Close, Taylor E.; Rose, Keeley; Ward, Roxanne; Mehl, M; Farrell, Catherine; Lacroix, Jacques; Creery, David; Kesselman, Murray; Stanimirovic, Danica; Hutchison, James S.

doi:10.1097/pcc.0b013e3181e8b32d

Cited by 89 publications

(72 citation statements)

References 37 publications

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“…These three biomarkers are involved in the pathogenesis of traumatic brain injury, and have also been shown to reflect the severity of neuronal injury. 52,53 Cord GFAP and UCHL1 levels correlate with the severity of HIE; however, only GFAP levels remained significantly higher in moderate to severe HIE at later time intervals, in contrast to UCHL1, which did not show any difference in relation to severity by 6 to 24 hours. 50 In infants who were treated with induced hypothermia, there was no significant difference in GFAP and UCLH1 levels during hypothermia and rewarming.…”

Section: Novel Biomarkers Of Brain Injurymentioning

confidence: 82%

Early predictors of outcome in infants treated with hypothermia for hypoxic–ischaemic encephalopathy

Merchant

Azzopardi

2015

Develop Med Child Neuro

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Hypoxic–ischaemic encephalopathy (HIE) is a leading cause of acquired neonatal brain injury. Assessment of the severity of cerebral injury and likely neurological outcome in infants with HIE is important for determining management and prognosis, for counselling parents, and for selection for neuroprotective trials. The condition of the infant at birth, the severity of HIE, neurophysiological tests, including amplitude‐integrated electroencephalography (aEEG), biochemical markers, and neuroimaging have been used to assess prognosis and predict long‐term outcome. The predictive accuracy of these indicators in the early postnatal period is modest. Neurophysiological assessment seems to be most helpful during the first 24 to 48 hours after birth whilst magnetic resonance imaging (MRI) seems most informative later. Several biochemical markers, including serum S100β and neuron‐specific enolase (NSE), are also associated with HIE but their levels depend on the timing of sampling and their prognostic value is uncertain. Comprehensive neurophysiological assessment and neuroimaging may be limited to specialist centres. Therapeutic hypothermia is now standard care in infants with moderate to severe HIE so it is important to examine the influence of hypothermia on the assessment of prognosis in these infants.

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Section: Novel Biomarkers Of Brain Injurymentioning

confidence: 82%

Early predictors of outcome in infants treated with hypothermia for hypoxic–ischaemic encephalopathy

Merchant

Azzopardi

2015

Develop Med Child Neuro

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“…However, when astrocytes are damaged, GFAP is released into the cerebrospinal fluid (CSF) as soluble fragments [6,8]. In humans, increased levels of GFAP in the CSF and blood have been reported with various neural diseases, for example, systemic lupus erythematosus, multiple sclerosis, Alzheimer's disease, subarachnoid hemorrhage and traumatic brain injury [3,16,17]. We postulated that GFAP may be released to peripheral blood in progressive myelomalacia following neural damage.…”

mentioning

confidence: 99%

Serum Glial Fibrillary Acidic Protein as a Diagnostic Biomarker in Dogs with Progressive Myelomalacia

Sato

Shimamura

Mashita

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. In humans, increased levels of GFAP in the CSF and blood have been reported with various neural diseases. However, there has been no study describing the usefulness of GFAP in the blood for disease of the spinal cord in dogs. The aim of this study was to describe the utility of GFAP in serum for a diagnosis of progressive myelomalacia. Fifty-six dogs with acute thoracolumbar IVDD diagnosed by computed tomography with myelography or MRI were included. Serum specimens were collected at initial presentation from all cases and at follow-up examinations from some cases. Serum samples were assayed for GFAP concentrations using a commercially available GFAP ELISA Kit. Progressive myelomalacia was the final diagnosis in 8/51 cases (15.6%). Eight dogs had clinical signs suggestive of progressive myelomalacia, of which 6 were positive and 2 were negative by GFAP. Seven dogs had a detectable level of serum GFAP, of which 6 had the onset of progressive myelomalacia. The sensitivity and specificity of the GFAP to progressive myelomalacia were 75% and 97.7%, respectively. The results suggest the utility of GFAP in serum in the diagnosis of progressive myelomalacia.

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“…Timing of blood sampling for biomarker assessments was also based on published clinical and pre-clinical reports [54][55][56][57][58][59][60][61][62][63][64][65] circulating biomarker levels and both behavioral and histopathological outcomes are presented in a separate manuscript focused on these unique biomarker applications. 26 As will become evident in the manuscripts that follow, the biomarker data generated by the OBTT consortium are quite unique and highly informative about biomarkers in the models studied.…”

Section: Page 19 Of 41mentioning

confidence: 99%

“…[54][55][56][57][58][59][60][61][62][63][64][65] However, our goal in designing our approach was to use biomarkers that had the greatest potential for translation to clinical use. To this end, in the grant proposal that was funded, we partnered with Banyan Biomarkers LLC and biomarker selection and sampling were guided by three affiliated scientists (RH, SM, and KW).…”

Section: Biomarkers and Biomarker Samplingmentioning

confidence: 99%

Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy

Kochanek

Bramlett

Dixon

et al. 2016

Journal of Neurotrauma

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Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan wars and the magnitude of its importance in the civilian setting is finally being recognized. Given the scope of the problem, new therapies are needed across the continuum of care. Few therapies have been shown to be successful. In severe TBI, current guidelines-based acute therapies are focused on the reduction of intracranial hypertension and optimization of cerebral perfusion. One factor considered important to the failure of drug development and translation in TBI relates to the recognition that TBI is extremely heterogeneous and presents with multiple phenotypes even within the category of severe injury. To address this possibility and attempt to bring the most promising therapies to clinical trials, we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug screening consortium for acute therapies in severe TBI. OBTT was developed to include a spectrum of established TBI models at experienced centers and assess the effect of promising therapies on both conventional outcomes and serum biomarker levels. In this review, we outline the approach to TBI modeling, evaluation of therapies, drug selection, and biomarker assessments for OBTT, and provide a framework for reports in this issue on the first five therapies evaluated by the consortium.

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Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum*

Cited by 89 publications

References 37 publications

Early predictors of outcome in infants treated with hypothermia for hypoxic–ischaemic encephalopathy

Early predictors of outcome in infants treated with hypothermia for hypoxic–ischaemic encephalopathy

Serum Glial Fibrillary Acidic Protein as a Diagnostic Biomarker in Dogs with Progressive Myelomalacia

Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy

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