Journal of neurotrauma
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Journal of neurotrauma · Sep 2011
Gene therapy for traumatic central nervous system injury and stroke using an engineered zinc finger protein that upregulates VEGF-A.
Recent studies have identified anti-apoptotic functions for vascular endothelial growth factor (VEGF) in the central nervous system (CNS). However, VEGF therapy has been hampered by a tendency to promote vascular permeability, edema, and inflammation. Recently, engineered zinc finger proteins (ZFPs) that upregulate multiple forms of VEGF in their natural biological ratios, have been developed to overcome these negative side effects. ⋯ Following pial strip of the forelimb motor cortex, brains treated with an adenovirus encoding VEGF ZFPs (AdV-ZFP) showed higher neuronal survival, accelerated wound contraction, and reduced lesion volume between 1 and 6 weeks after injury. Behavioral testing using the cylinder test for vertical exploration showed that AdV-VEGF-ZFP treatment enhanced contralateral forelimb function within the first 2 weeks after injury. Our results indicate that VEGF ZFP therapy is neuroprotective following traumatic injury or stroke in the adult mammalian CNS.
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Journal of neurotrauma · Sep 2011
Multicenter StudyNatural history of headache after traumatic brain injury.
Headache is one of the most common persisting symptoms after traumatic brain injury (TBI). Yet there is a paucity of prospective longitudinal studies of the incidence and prevalence of headache in a sample with a range of injury severity. We sought to describe the natural history of headache in the first year after TBI, and to determine the roles of prior history of headache, sex, and severity of TBI as risk factors for post-traumatic headache. ⋯ Overall, headache is common in the first year after TBI, independent of the severity of injury range examined in this study. Use of the International Classification of Headache Disorders criteria requiring onset of headache within 1 week of injury underestimates rates of post-traumatic headache. Better understanding of the natural history of headache including timing, type, and risk factors should aid in the design of treatment studies to prevent or reduce the chronicity of headache and its disruptive effects on quality of life.
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Journal of neurotrauma · Sep 2011
Altered obstacle negotiation after low thoracic hemisection in the cat.
Following a lateralized spinal cord injury (SCI) in humans, substantial walking recovery occurs; however, deficits persist in adaptive features of locomotion critical for community ambulation, including obstacle negotiation. Normal obstacle negotiation is accomplished by an increase in flexion during swing. If an object is unanticipated or supraspinal input is absent, obstacle negotiation may involve the spinally organized stumbling corrective response. ⋯ Therefore, following complete severing of half of the spinal cord, the ability to modify ipsilateral hindlimb trajectory shows significant recovery and by 16 weeks permits effective clearing of an obstacle, without contact, ∼50% of the time. Although this suggests plasticity of supporting circuitry, it is insufficient to support consistent clearance. This inconsistency, even at the most chronic time point assessed (16 weeks), is probably a contributing factor to falls reported for people with SCI.
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Journal of neurotrauma · Sep 2011
The association between apolipoprotein E and traumatic brain injury severity and functional outcome in a rehabilitation sample.
Traumatic brain injury (TBI) can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E (ApoE) genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. ⋯ Prediction of worse Glasgow Outcome Scale-Extended (GOSE) scores for ɛ4 carriers was supported with greater susceptibility seen in females. These results indicate the ApoE ɛ4 allele may be associated with poorer long-term outcome, but not acute injury severity. Possible mechanisms include differential effects of the ɛ4 allele on inflammatory and cellular repair processes, and/or amyloid deposition.
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Journal of neurotrauma · Sep 2011
Ethanol intoxication is associated with a lower incidence of admission coagulopathy in severe traumatic brain injury patients.
The aim of this study was to determine the impact of ethanol (ETOH) on the incidence of severe traumatic brain injury (sTBI)-associated coagulopathy and to examine the effect of ETOH on in-hospital outcomes in patients sustaining sTBI. Patients admitted to the surgical intensive care unit from June 2005 through December 2008 following sTBI, defined as a head Abbreviated Injury Scale (AIS) score ≥3, were retrospectively identified. Patients with a chest, abdomen, or extremity AIS score >3 were excluded to minimize the impact of extracranial injuries. ⋯ ETOH (+) patients had a significantly lower in-hospital mortality rate than ETOH (-) patients [9.8% versus 16.6%; adjusted p=0.011; adjusted OR (95% CI)=0.39 (0.19,0.81)]. For brain-injured patients arriving alive to the hospital, ETOH intoxication is associated with a significantly lower incidence of early coagulopathy and in-hospital mortality. Further research to establish the pathophysiologic mechanisms underlying any potential beneficial effect of ETOH on the coagulation system following sTBI is warranted.