Journal of neurotrauma
-
Journal of neurotrauma · Nov 2022
Increased fear generalization and amygdala AMPA receptor proteins in chronic traumatic brain injury.
Cognitive impairments and emotional lability are common long-term consequences of traumatic brain injury (TBI). How TBI affects interactions between sensory, cognitive, and emotional systems may reveal mechanisms that underlie chronic mental health comorbidities. Previously, we reported changes in auditory-emotional network activity and enhanced fear learning early after TBI. ⋯ These findings suggest that TBI precipitates maladaptive associative fear generalization rather than non-associative sensitization. Basolateral amygdala (BLA) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAr) subunits GluA1 and GluA2 levels were analyzed and the FPI-Noise Shock group had increased GluA1 (but not GluA2) levels that correlated with the level of tone fear generalization. This study illustrates a unique chronic TBI phenotype with both a cognitive impairment and increased fear and possibly altered synaptic transmission in the amygdala long after TBI, where stimulus generalization may underlie maladaptive fear and hyperarousal.
-
Journal of neurotrauma · Nov 2022
Comparison Groups Matter in Traumatic Brain Injury Research: An Example with Dementia.
The association between traumatic brain injury (TBI) and risk for Alzheimer disease and related dementias (ADRD) has been investigated in multiple studies, yet reported effect sizes have varied widely. Large differences in comorbid and demographic characteristics between individuals with and without TBI could result in spurious associations between TBI and poor outcomes, even when control for confounding is attempted. Yet, inadvertent control for post-TBI exposures (e.g., psychological and physical trauma) could result in an underestimate of the effect of TBI. ⋯ Using data on Veterans aged ≥55 years obtained from the Veterans Health Administration (VA) for years 1999-2019, we compared risk of ADRD between Veterans with incident TBI (n = 9440) and (1) the general population of Veterans who receive care at the VA (All VA) (n = 119,003); (2) Veterans who received care at a VA emergency department (VA ED) (n = 111,342); and (3) Veterans who received care at a VA ED for non-TBI trauma (VA ED NTT) (n = 65,710). In inverse probability of treatment weighted models, TBI was associated with increased risk of ADRD compared with All VA (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.84, 2.04), VA ED (HR 1.42; 95% CI 1.35, 1.50), and VA ED NTT (HR 1.12; 95% CI 1.06, 1.18). The estimated effect of TBI on incident ADRD was strongly impacted by choice of the comparison group.
-
Journal of neurotrauma · Nov 2022
Risk factors for high symptom burden 3 months after traumatic brain injury and implications for clinical trial design: a TRACK-TBI study.
More than 75% of patients presenting to level I trauma centers in the United States with suspicion of TBI sufficient to require a clinical computed tomography scan report injury-related symptoms 3 months later. There are currently no approved treatments, and few clinical trials have evaluated possible treatments. Efficient trials will require subject inclusion and exclusion criteria that balance cost-effective recruitment with enrolling individuals with a higher chance of benefiting from the interventions. ⋯ TBI severity was not significantly associated with 3-month symptom burden (p = 0.37). Using simulated data to evaluate the effect of enrichment, we showed that including only people with high symptom burden at 2 weeks would permit trials to reduce the sample size by half, with minimal increase in screening, as compared with enrolling an unenriched sample. Clinical trials aimed at reducing symptoms after TBI can be efficiently conducted by enriching the included sample with people reporting a high early symptom burden.
-
Journal of neurotrauma · Nov 2022
Understanding primary blast injury: High frequency pressure acutely disrupts neuronal network dynamics in cerebral organoids.
Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The primary neurophysiological response to blast-induced pressure waveforms remains poorly understood. ⋯ Conversely, organoids exposed to higher amplitude pressure (350k Pa) displayed drastic neurophysiological differences that failed to recover within 24 h. Further, lower amplitude "blast" (250 kPa) did not induce cellular damage whereas the higher amplitude "blast" (350 kPa) generated greater apoptosis throughout each organoid. Our data indicate that specific features of pressure waves found intracranially during blast TBI have varied effects on neurophysiological activity that can occur even without cellular damage.
-
Journal of neurotrauma · Nov 2022
Females Exhibit Better Cerebral Pressure Autoregulation, Less Mitochondrial Dysfunction, and Reduced Excitotoxicity following Severe Traumatic Brain Injury.
The aim of the study was to investigate sex-related differences in intracranial pressure (ICP) dynamics, cerebral pressure autoregulation (PRx55-15), cerebral energy metabolism, and clinical outcome after severe traumatic brain injury (TBI). One-hundred sixty-nine adult patients with TBI, treated at the Neurointensive Care (NIC) Unit at Uppsala University Hospital between 2008 and 2020 with ICP and cerebral microdialysis (MD) monitoring were included. Of the 169 patients with TBI, 131 (78%) were male and 38 (22%) female. ⋯ There was no difference in mortality or the degree of favorable outcome between the sexes. Altogether, females exhibited more favorable cerebral physiology post-TBI, particularly better mitochondrial function and reduced excitotoxicity, but this did not translate into better clinical outcome compared with males. Future studies are needed to further explore potential sex differences in secondary injury mechanisms in TBI.