Journal of neurotrauma
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Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. ⋯ In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.
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Journal of neurotrauma · Dec 2010
Focal neuronal damage in patients with neuropsychological impairment after diffuse traumatic brain injury: evaluation using ¹¹C-flumazenil positron emission tomography with statistical image analysis.
This study was conducted to identify the regional neuronal damage occurring in patients with neuropsychological impairment following diffuse traumatic brain injury (TBI) compared with normal control subjects. In addition, measures of the neuropsychological tests were correlated with regional ¹¹C-flumazenil (FMZ) binding potential (BP) reductions to clarify the relationship between cognitive impairment and regional neuronal damage. We performed ¹¹C-flumazenil positron emission tomography (FMZ-PET) studies using three-dimensional stereotactic surface projection (3D-SSP) statistical image analysis in eight diffuse axonal injury (DAI) patients (mean age 29.1 ± 11.1 years, range 19-46 years). ⋯ FIQ, verbal IQ (VIQ), and PIQ also negatively correlated with the BZR index in the left medial frontal gyrus. DAI uniformly induced neuronal damage in the medial frontal cortex and the thalamus, which may be related to underlying cognitive impairments in diffuse TBI patients. Future studies to confirm a common area of focal neuronal damage and a direct correlation with neuropsychological testing may validate the use of FMZ-PET for the functional diagnosis of neuropsychological impairments after TBI.
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Journal of neurotrauma · Dec 2010
Reorganization of motor cortex after controlled cortical impact in rats and implications for functional recovery.
We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. ⋯ Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery.
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Journal of neurotrauma · Dec 2010
Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits.
Traumatic brain injury (TBI) patients are known to be at high risk for venous thromboembolic events (VTEs). The Brain Trauma Foundation Guidelines (2007) state that low-molecular-weight heparin or unfractionated heparin should be used to prevent VTE complications, but suggest that there is an increased risk of expansion of intracranial hemorrhages (ICH) with VTE prophylaxis. In addition, it is unclear which treatment regimen (i.e., medication, dose, and timing) provides the best risk:benefit ratio in TBI patients. ⋯ Importantly, only one patient suffered a symptomatic expansion of ICH while on VTE prophylaxis, at 15 days post-trauma. These results suggest that current regimens of VTE prophylaxis used in our TBI population provide a relatively high level of protection against VTEs, and an extremely low risk of expanding ICH. They also suggest that there was no difference in VTE between dalteparin- and enoxaparin-treated patients.
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Journal of neurotrauma · Dec 2010
Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats.
Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1. ⋯ The ¹³C glucose enrichment of the C3 position of glutamate (C3) in neurons was significantly decreased ipsilateral to FPI at day 14, whereas the enrichment of glutamine in astrocytes had returned to sham levels at this time point. These findings indicate that the oxidative metabolism of glucose is reduced to a greater extent in neurons compared to astrocytes following a FPI. The increased utilization of acetate to synthesize glutamine, and the acetate enrichment of glutamate via the glutamate-glutamine cycle, suggests an integral protective role for astrocytes in maintaining metabolic function following TBI-induced impairments in glucose metabolism.