Journal of neurotrauma
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Journal of neurotrauma · Jan 2016
Beneficial effects of early mTORC1 inhibition after traumatic brain injury.
The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway mediates many aspects of cell growth and regeneration and is upregulated after moderate to severe traumatic brain injury (TBI). The significance of this increased signaling event for recovery of brain function is presently unclear. ⋯ We suppressed this peak activity by a single injection of the mTORC1 inhibitor rapamycin 1 h after CCI and showed that this acute treatment significantly diminishes the extent of neuronal death, astrogliosis, and cognitive impairment 1-3 days after injury. Our findings suggest that the early neuronal peak of mTORC1 activity after TBI is deleterious to brain function, and that acute, early intervention with mTORC1 inhibitors after injury may represent an effective form of treatment to improve recovery in human patients.
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Journal of neurotrauma · Jan 2016
Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury.
The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. ⋯ The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury.
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Journal of neurotrauma · Jan 2016
Early CT frontal abnormalities predict long term neurobehavioral problems but not affective problems after moderate to severe TBI.
Behavioral problems are serious consequences of moderate to severe traumatic brain injury (TBI) and have a negative impact on outcome. There may be two types: neurobehavioral problems, manifesting as inadequate social behavior resulting from prefrontal system damage, and affective behavioral problems, resulting from emotional distress as a reaction to the brain injury. In the present study we investigated whether these two types of behavioral problems, as indicated by proxies, could be distinguished in a group of chronic TBI patients and whether early indicators of prefrontal damage on imaging could predict long-term neurobehavioral problems. ⋯ Long-term neurobehavioral problems were significantly correlated to one-year outcome and return to work in the long term. We conclude that in patients with moderate to severe TBI neurobehavioral and affective problems can be distinguished. Early CT frontal abnormalities predict long-term neurobehavioral problems, but not affective problems.
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Journal of neurotrauma · Jan 2016
Neuroprotective effects of Co-ultraPEALut on secondary inflammatory process and autophagy involved in traumatic brain injury.
Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. In the present study, we performed a widely used model of TBI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound Co-ultraPEALut. We demonstrated that the treatment with Co-ultraPEALut resulted in a significant improvement of motor and cognitive recovery after controlled cortical impact, as well as markedly reducing lesion volumes. ⋯ In addition, treatment with Co-ultraPEALut significantly enhanced the post-TBI expression of the neuroprotective neurotrophins glial cell line-derived neurotrophic factor compared with vehicle. Co-ultraPEALut at the dose of 1 mg/kg also modulated apoptosis, the release of cytokine and reactive oxygen species, the activation of chymase, tryptase, and nitrotyrosine, and inhibited autophagy. Thus, our data demonstrated that Co-ultraPEALut at a lower dose compared with PEA alone can exert neuroprotective effects and the combination of both could improve their ability to counteract the neurodegeneration and neuroinflammation induced by TBI.
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Journal of neurotrauma · Jan 2016
Differences in Regional Brain Volumes Two Months and One Year after Mild Traumatic Brain Injury.
Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. ⋯ These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.