Journal of neurotrauma
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Journal of neurotrauma · Aug 2012
An FMRI study of auditory orienting and inhibition of return in pediatric mild traumatic brain injury.
Studies in adult mild traumatic brain injury (mTBI) have shown that two key measures of attention, spatial reorienting and inhibition of return (IOR), are impaired during the first few weeks of injury. However, it is currently unknown whether similar deficits exist following pediatric mTBI. The current study used functional magnetic resonance imaging (fMRI) to investigate the effects of semi-acute mTBI (<3 weeks post-injury) on auditory orienting in 14 pediatric mTBI patients (age 13.50±1.83 years; education: 6.86±1.88 years), and 14 healthy controls (age 13.29±2.09 years; education: 7.21±2.08 years), matched for age and years of education. ⋯ In contrast, functional imaging results indicated that patients with mTBI demonstrated significantly decreased activation within the bilateral posterior cingulate gyrus, thalamus, basal ganglia, midbrain nuclei, and cerebellum. The spatial topography of hypoactivation was very similar to our previous study in adults, suggesting that subcortical structures may be particularly affected by the initial biomechanical forces in mTBI. Current results also suggest that fMRI may be a more sensitive tool for identifying semi-acute effects of mTBI than the procedures currently used in clinical practice, such as neuropsychological testing and structural scans. fMRI findings could potentially serve as a biomarker for measuring the subtle injury caused by mTBI, and documenting the course of recovery.
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Journal of neurotrauma · Aug 2012
Predicting progressive hemorrhagic injury after traumatic brain injury: derivation and validation of a risk score based on admission characteristics.
Previous studies have demonstrated that patients with traumatic brain injury (TBI) who also have progressive hemorrhagic injury (PHI), have a higher risk of clinical deterioration and worse outcomes than do TBI patients without PHI. Therefore, the early prediction of PHI occurrence is useful to evaluate the status of patients with TBI and to improve outcomes. The objective of this study was to develop and validate a prognostic model that uses information available at admission to determine the likelihood of PHI after TBI. ⋯ In the validation cohort, the corresponding PHI rates were 10.9%, 47.3%, and 86.9%. The C-statistic for the point system was 0.864 (p=0.509 by the Hosmer-Lemeshow test) in the development cohort, and 0.862 (p=0.589 by the Hosmer-Lemeshow test) in the validation cohort. In conclusion, a relatively simple risk score using admission predictors accurately predicted the risk for PHI after TBI.
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Journal of neurotrauma · Aug 2012
Acute molecular perturbation of inducible nitric oxide synthase with an antisense approach enhances neuronal preservation and functional recovery after contusive spinal cord injury.
Inducible nitric oxide synthase (iNOS) is a key mediator of inflammation and oxidative stress produced during pathological conditions, including neurodegenerative diseases and central nervous system (CNS) injury. iNOS is responsible for the formation of high levels of nitric oxide (NO). The production of highly reactive and cytotoxic NO species, such as peroxynitrite, plays an important role in secondary tissue damage. We have previously demonstrated that acute administration of iNOS antisense oligonucleotides (ASOs) 3 h after moderate contusive spinal cord injury (SCI) potently inhibits iNOS-mediated increases in NO levels, leading to reduced blood-spinal cord barrier permeability, decreased neutrophil accumulation, and less neuronal cell death. ⋯ Although animals treated with iNOS ASOs demonstrated no significant differences in BBB scores compared to controls, subscore analysis revealed a significant improvement in foot positioning, trunk stability, and tail clearance. Histologically, while no gross improvement in preserved white and gray matter was observed, greater numbers of surviving neurons were present adjacent to the lesion site in iNOS ASO-treated animals than controls. These results support the effectiveness of targeting iNOS acutely as a therapeutic approach after SCI.
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In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. ⋯ This increase was associated with an increase in phospho-CREB levels (p<0.021), and brain-derived neurotrophic factor (BDNF) expression (p<0.0006). In conclusion, estrone given acutely after injury increases the signaling of protective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.
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Journal of neurotrauma · Aug 2012
The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats.
For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. ⋯ Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients.