Journal of neurotrauma
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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.
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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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Traumatic brain injury (TBI) in early to mid-life is associated with an increased risk of dementia in late life. It is unclear whether TBI results in acceleration of Alzheimer's disease (AD)-like pathology or has features of another dementing condition, such as chronic traumatic encephalopathy, which is associated with more-prominent mood, behavior, and motor disturbances than AD. Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set was obtained over a 5-year period. ⋯ We conclude that TBI with chronic deficit or dysfunction is associated with an increased odds ratio for dementia. Clinically, patients with dementia associated with TBI were more likely to have symptoms of depression, agitation, irritability, and motor dysfunction than patients with probable AD. These findings suggest that dementia in individuals with a history of TBI may be distinct from AD.
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Journal of neurotrauma · Jul 2013
Brain-derived protein concentrations in the cerebrospinal fluid: contribution of trauma resulting from ventricular drain insertion.
In recent years, the measurement of biomarkers following neurotrauma assisted in improving outcome prediction and guiding therapy. The use of neuroproteins as diagnostic parameters requires a detailed knowledge of their dynamics in biological fluids for an appropriate interpretation. S100B is the most widely studied neuromarker, and its concentration in serum and cerebrospinal fluid (CSF) reflects the extent of brain damage. ⋯ Beta-Trace concentrations in the CSF were not altered by EVD insertion. Our data demonstrate that EVD insertion results in a distinct increase of S100B and NSE concentrations in the CSF. Thus, the tampering of brain-derived protein concentrations in the CSF by diagnostic or therapeutic procedures has to be considered in the interpretation of neuromarker levels.