Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury

Korley, Frederick K.; Wu, Alan H.B.; Yue, John K.; Manley, Geoffrey T.; Sair, Haris I.; Eyk, Jennifer E. Van; Okonkwo, David O.; Valadka, Alex B.; Gordon, Wayne A.; Maas, Andrew I. R.; Mukherjee, Pratik; Yuh, Esther L.; Lingsma, Hester F.; Puccio, Ava M.; Schnyer, David M.

doi:10.1089/neu.2015.3949

Cited by 120 publications

(94 citation statements)

References 71 publications

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“…Simon et al, 2016 reported no predictive value for BDNF to discriminate survival and nonsurvival patients 37. Similar to our findings, day‐of‐injury serum BDNF was associated with TBI diagnosis; however, the authors also showed 6‐month prognostic value regarding recovery from TBI 38. Further, the CSF levels of BDNF predicted mortality within 7 days of hospitalization after severe TBI 39.…”

Section: Discussionsupporting

confidence: 81%

Elevated glutamate and lactate predict brain death after severe head trauma

Stefani

Modkovski

Hansel

et al. 2017

Ann Clin Transl Neurol

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ObjectiveClinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.MethodsThis cross‐sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, n = 6) or survival (survival, n = 14), within 3 days after hospital admission. CSF levels of brain‐derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed.ResultsGlutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55–98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55–98.08%). BDNF and GDNF did not discriminate poor outcome.InterpretationThis early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI.

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Section: Discussionsupporting

confidence: 81%

Elevated glutamate and lactate predict brain death after severe head trauma

Stefani

Modkovski

Hansel

et al. 2017

Ann Clin Transl Neurol

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“…Future investigation will examine how biomarkers correlate with functional changes observed on imaging and behavioral changes detected on exam. Korley and colleagues found significant serum changes of brain-derived neurotrophic factor in children with functional imaging changes following TBI indicating increased susceptibility for depression [107]. Further studies are necessary to determine if sensory processing deficits are linked to changes in mood.…”

Section: Advanced Imaging Correlationsmentioning

confidence: 99%

Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms

Singh

Turner

Nguyen

et al. 2016

Behavioural Neurology

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Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD.

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“…This finding adds to other literature in the field that drops in BDNF may serve as a viable biomarker of concussion. For example, Korley et al (2016) found that BDNF levels were significantly lower in mild TBI cases compared to moderate and severe TBI when assessed on the day of the injury. Additionally, they reported that lower BDNF levels following mTBI was predictive of poorer outcomes at a 6-month follow-up.…”

Section: Discussionmentioning

confidence: 99%

New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats

Wirth

Kimball

et al. 2017

Journal of Neuroscience Methods

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Background Mild traumatic brain injuries (mTBI) are an increasing health concern due to persistent behavioral and neurological effects. To better understand these effects, researchers frequently rely on animal injury models. Existing models, however, may not adequately reproduce the mechanism of injury as it occurs in humans. New Method Our new model for inducing mTBI in rodents entails acceleration of the animal toward a stationary impact zone to produce rapid rotational movement of the head. The aim of the present experiment was to characterize the effects of this injury in female and male rats on behavior, cognition, and neural plasticity. Results mTBI produced the most widespread effects in females: they were more active during recovery within minutes of mTBI and more active in the center of the open field 4 days after mTBI. Spatial learning deficits in the water maze were mild but persistent and accompanied by reduced numbers of immature neurons in the hippocampus along with reductions in sera levels of the neurotrophin, BDNF. By contrast, male mTBI rats mainly exhibited mild spatial learning deficits, with no other observed effects. Comparison with Existing Methods Our model induced effects on behavior and biology in rats that aligned with existing models. However, new patterns were observed, particularly when comparing females and males. Conclusions Taken together, these findings confirm the validity of this model and point to key differences between females and males in symptom severity and type. Additionally, our model adds a novel injury mechanism that complements existing rodent models.

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Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury

Cited by 120 publications

References 71 publications

Elevated glutamate and lactate predict brain death after severe head trauma

Elevated glutamate and lactate predict brain death after severe head trauma

Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms

New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats

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