Journal of neurotrauma
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Journal of neurotrauma · Oct 2017
Does normobaric hyperoxia cause oxidative stress in the injured brain? A microdialysis study using 8-iso-PGF2α as a biomarker.
Significant controversy exists regarding the potential clinical benefit of normobaric hyperoxia (NBO) in patients with traumatic brain injury (TBI). This study consisted of two aims: 1) to assess whether NBO improves brain oxygenation and metabolism and 2) to determine whether this therapy may increase the risk of oxidative stress (OxS), using 8-iso-Prostaglandin F2α (PGF2α) as a biomarker. Thirty-one patients with a median admission Glasgow Coma Scale score of 4 (min: 3, max: 12) were monitored with cerebral microdialysis and brain tissue oxygen sensors and treated with fraction of inspired oxygen (FiO2) of 1.0 for 4 h. ⋯ In the five patients with brain lactate concentration ([Lac]brain) > 3.5 mmol/L at baseline, NBO induced a marked reduction in both [Lac]brain and lactate-to-pyruvate ratio. Although these differences were not statistically significant, together with the results of our previous study, they suggest that TBI patients would benefit from receiving NBO when they show indications of disturbed brain metabolism. These findings, in combination with increasing evidence that TBI metabolic crises are common without brain ischemia, open new possibilities for the use of this accessible therapeutic strategy in TBI patients.
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Journal of neurotrauma · Oct 2017
The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.
While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). ⋯ Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.
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Journal of neurotrauma · Oct 2017
Frontal TBI increases impulsive decision making in rats: A potential role for the inflammatory cytokine interleukin-12.
Traumatic brain injury (TBI) is associated with the development of numerous psychiatric diseases. Of particular concern for TBI patients is the impact of chronic impulsivity on daily functioning. Despite the scope of the human problem, little has been done to address impulsivity in animal models of brain injury. ⋯ Whereas a significant lesion was only evident in severely injured rats, analysis of cytokine levels within the frontal cortex revealed a selective increase in interleukin (IL)-12 that was associated with the magnitude of the change in impulsive choice caused by both milder and severe TBI. These findings suggest that tissue loss alone cannot explain the increased impulsivity observed, and that inflammatory pathways mediated by IL-12 may be a contributing factor. The findings from this study highlight the sensitivity of sophisticated behavioral measures designed to assess neuropsychiatric dysfunction in the detection of TBI-induced cognitive impairments and their utility in identifying potential mechanistic pathways and therapeutic targets.
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Journal of neurotrauma · Oct 2017
Recovery from coma post-cardiac arrest is dependent on the orexin pathway.
Cardiac arrest (CA) affects >550,000 people annually in the United States whereas 80-90% of survivors suffer from a comatose state. Arousal from coma is critical for recovery, but mechanisms of arousal are undefined. Orexin-A, a hypothalamic excitatory neuropeptide, has been linked to arousal deficits in various brain injuries. ⋯ This is of considerable clinical interest given that suvorexant recently received U. S. Food and Drug Administration approval for insomnia treatment.
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Journal of neurotrauma · Oct 2017
Bone marrow-derived endothelial progenitor cell treatment in a model of lateral fluid percussion injury in rats: Evaluation of acute and subacute outcome measures.
Traumatic brain injury (TBI) continues to be a serious health care issue while therapies to treat TBI remain elusive. Promising results from the use of endothelial progenitor cells (EPCs) in numerous disease states highlight the pleiotropic capacity of this cell type. We have previously demonstrated that EPC-conditioned media reduces axonal degeneration subsequent to in vitro oxygen-glucose deprivation insult and concurrently improves white matter and microvascular outcome in vivo after mid-line fluid percussion injury. ⋯ Behavioral testing using the Morris Water Maze and rotarod demonstrated significant improvement in locomotor function, as measured by the rotarod task, but no significant differences in spatial memory ability. The data suggest that EPCs contribute to improvements in the early phase of secondary injury through inhibition of apoptosis whereas the effects on longer-term recovery were less clearly defined. There is potential in the use of EPCs to treat secondary injury post-TBI; however, optimization of their effects through increased duration or homing capacities remains to be examined.