Journal of neurotrauma
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Journal of neurotrauma · Jul 2013
ReviewSystems biology approaches for discovering biomarkers for traumatic brain injury.
The rate of traumatic brain injury (TBI) in service members with wartime injuries has risen rapidly in recent years, and complex, variable links have emerged between TBI and long-term neurological disorders. The multifactorial nature of TBI secondary cellular response has confounded attempts to find cellular biomarkers for its diagnosis and prognosis or for guiding therapy for brain injury. ⋯ In addition, we describe opportunities for applying this methodology to existing TBI data sets to identify new biomarker candidates and gain insights about the underlying molecular mechanisms of TBI response. As an exemplar, we apply network and pathway analysis to a manually compiled list of 32 protein biomarker candidates from the literature, recover known TBI-related mechanisms, and generate hypothetical new biomarker candidates.
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Journal of neurotrauma · Jul 2013
Triage of children with moderate and severe traumatic brain injury to trauma centers.
Outcomes after pediatric traumatic brain injury (TBI) are related to pre-treatment factors including age, injury severity, and mechanism of injury, and may be positively affected by treatment at trauma centers relative to non-trauma centers. This study estimated the proportion of children with moderate to severe TBI who receive care at trauma centers, and examined factors associated with receipt of care at adult (ATC), pediatric (PTC), and adult/pediatric trauma centers (APTC), compared with care at non-trauma centers (NTC) using a nationally representative database. The Kids' Inpatient Database was used to identify hospitalizations for moderate to severe pediatric TBI. ⋯ Multiple regression analyses showed receipt of care at a trauma center was associated with age and polytrauma. We concluded that almost 84% of children with moderate to severe TBI currently receive care at a Level I or Level II trauma center. Children with trauma to multiple body regions in addition to more severe TBI are more likely to receive care a trauma center relative to a NTC.
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Journal of neurotrauma · Jul 2013
Service utilization among Iraq and Afghanistan veterans screening positive for traumatic brain injury.
We compared mental health outpatient, primary care, and emergency care service utilization among veterans screening TBI positive (S-TBI⁺) versus those screening TBI negative (S-TBI⁻) and describe associations between TBI-related symptoms and health service utilization. Our study population consisted of 1746 Iraq and Afghanistan veterans in VA care screened for TBI between April 1, 2007 and June 1, 2010. Rates of mental health outpatient, primary care, and emergency services utilization were greater for S-TBI(+) veterans, compared with S-TBI(-) veterans, even after adjusting for mental health screen results. ⋯ Reports of dizziness (IRR, 1.24; 95% CI, 1.02-1.51; p<0.05) and headaches (IRR, 1.41; 95% CI, 1.16-1.7; p<0.001) were associated with increased primary care utilization rates. Higher utilization rates among veterans who screened positive for TBI were not better explained by screening positive for comorbid mental health problems. Knowing that certain symptoms are more strongly associated with increased utilization in certain health service domains will help to better plan for the care of returning veterans who screen positive for TBI.
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Journal of neurotrauma · Jul 2013
Hypothermia and pharmacological regimens that prevent overexpression and overactivity of the extracellular calcium-sensing receptor protect neurons against traumatic brain injury.
Traumatic brain injury (TBI) leads to acute functional deficit in the brain. Molecular events underlying TBI remain unclear. In mouse brains, we found controlled cortical impact (CCI) injury induced overexpression of the extracellular calcium-sensing receptor (CaSR), which is known to stimulate neuronal activity and accumulation of intracellular Ca(2+) and concurrent down-regulation of type B or metabotropic GABA receptor 1 (GABA-B-R1), a prominent inhibitory pathway in the brain. ⋯ Mild hypothermia, an established practice of neuroprotection for brain ischemia, partially but significantly blunted all of the above effects of CCI. Administration of CaSR antagonist NPS89636 mimicked hypothermia to reduce loss of brain tissue and motor functions in the CCI mice. These data together support the concept that CaSR overexpression and overactivity play a causal role in potentiating TBI potentially by stimulating excitatory neuronal responses and by interfering with inhibitory GABA-B-R signaling and that the CaSR could be a novel target for neuroprotection against TBI.
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Journal of neurotrauma · Jul 2013
Proton MR spectroscopy correlates diffuse axonal abnormalities with post-concussive symptoms in mild traumatic brain injury.
There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal abnormalities quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (¹H-MRSI) correlated with patients' PCS, we retrospectively studied 26 mTBI patients (mean Glasgow Coma Scale [GCS] score of 14.7), 18- to 56-year-olds and 13 controls three to 55 days post-injury. All were scanned at 3 Tesla with T1- and T2-weighted MRI and 3D ¹H-MRSI (480 voxels over 360 cm³, ∼30% of the brain). ⋯ The PCS-positive patients (n=15) had lower WM NAA than the controls (n=12; 7.0 ± 0.6 versus 7.9 ± 0.5mM; p=0.0007). Global WM NAA, therefore, showed sensitivity to the TBI sequelae associated with common PCS in patients with mostly normal neuroimaging, as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.