Journal of neurotrauma
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Journal of neurotrauma · Jan 2015
Altered regulation of protein kinase A activity in the medial prefrontal cortex of normal and brain injured animals actively engaged in a working memory task.
Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signaling is required for short- and long-term memory. In contrast, enhanced PKA activity has been shown to impair working memory, a prefrontal cortex (PFC)-dependent, transient form of memory critical for cognition and goal-directed behaviors. Working memory can be impaired after traumatic brain injury (TBI) in the absence of overt damage to the PFC. ⋯ Inhibition of PKA activity by intra-mPFC administration of Rp-cAMPS into TBI animals had no influence on working memory performance 30 min postinfusion, but significantly improved working memory when tested 24 h later. This improvement was associated with reduced glutamic acid decarboxylase 67 messenger RNA levels. Taken together, these results suggest that TBI-associated working memory dysfunction may result, in part, from enhanced PKA activity, possibly leading to altered expression of plasticity-related genes in the mPFC.
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Journal of neurotrauma · Jan 2015
GENETIC ACTIVATION OF mTORC1 SIGNALING WORSENS NEUROCOGNITIVE OUTCOME AFTER TRAUMATIC BRAIN INJURY.
Although the mechanisms that contribute to the development of traumatic brain injury (TBI)-related deficits are not fully understood, it has been proposed that altered energy utilization may be a contributing factor. The tuberous sclerosis complex, a heterodimer composed of hamartin/Tsc-1 and tuberin/Tsc-2, is a critical regulatory node that integrates nutritional and growth signals to govern energy using processes by regulating the activity of mechanistic Target of Rapamycin complex 1 (mTORC1). mTORC1 activation results in enhanced protein synthesis, an energy consuming process. ⋯ This enhanced level of increased mTORC1 activity was associated with worsened cognitive function as assessed using the Morris water maze and context discrimination tasks. These results suggest that there is a threshold of increased mTORC1 activity after a TBI that is detrimental to neurobehavioral performance, and interventions to inhibit excessive mTORC1 activation may be beneficial to neurocognitive outcome.
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Journal of neurotrauma · Jan 2015
Identification of hematomas in mild traumatic brain injury using an index of quantitative brain electrical activity.
Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment. ⋯ Sensitivity to hematomas was found to be 95.7% (95% CI = 85.2, 99.5), specificity was 43.9% (95% CI = 38.0, 49.9). There was no significant relationship between the TBI-Index and distance of the bleed from recording sites (F = 0.044, p = 0.833), or volume of blood measured F = 0.179, p = 0.674). Results of this study are a validation and extension of previously published retrospective findings in an independent population, and provide evidence that a TBI-Index for structural brain injury is a highly sensitive measure for the detection of potentially life-threatening traumatic intracranial hematomas, and could contribute to the rapid, quantitative evaluation and treatment of such patients.
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Journal of neurotrauma · Jan 2015
Randomized Controlled TrialTelephone and In-Person Cognitive Behavioral Therapy for Major Depression after Traumatic Brain Injury: A Randomized Controlled Trial.
Major depressive disorder (MDD) is prevalent after traumatic brain injury (TBI); however, there is a lack of evidence regarding effective treatment approaches. We conducted a choice-stratified randomized controlled trial in 100 adults with MDD within 10 years of complicated mild to severe TBI to test the effectiveness of brief cognitive behavioral therapy administered over the telephone (CBT-T) (n = 40) or in-person (CBT-IP) (n = 18), compared with usual care (UC) (n = 42). Participants were recruited from clinical and community settings throughout the United States. ⋯ CBT participants reported significantly more symptom improvement (p = 0.010) and greater satisfaction with depression care (p < 0.001), than did the UC group. In-person and telephone-administered CBT are acceptable and feasible in persons with TBI. Although further research is warranted, telephone CBT holds particular promise for enhancing access and adherence to effective depression treatment.
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Journal of neurotrauma · Jan 2015
Analysis of S100B serum levels in different types of traumatic intracranial lesions.
The objective of this study was to determine whether the type of intracranial traumatic lesions, the number of simultaneous traumatic lesions, and the occurrence of skull and facial bone fractures have an influence on S100 calcium binding protein B (S100B) serum levels. Patients with blunt traumatic brain injury were prospectively enrolled into this cohort study over a period of 13 months. Venous blood samples were obtained prior to emergency cranial CT scan in all patients within 3 h after injury. ⋯ In patients with intracranial traumatic lesions, skull fractures, as well as skull and facial bone fractures occurring together, were identified as significant additional factors for the increase in serum S100B levels (p < 0.0001). Older age was also associated with elevated S100B serum levels (p < 0.0001). Our data show that peak S100B serum levels were found in patients with cerebral edema and brain contusions.