Dataset Information

Long-Term Effects of Traumatic Brain Injury on Anxiety-Like Behaviors in Mice: Behavioral and Neural Correlates.

ABSTRACT: Traumatic brain injury (TBI) has been frequently linked to affective disorders such as anxiety and depression. However, much remains to be understood about the underlying molecular and signaling mechanisms that mediate affective dysfunctions following injury. A lack of consensus in animal studies regarding what the affective sequelae of TBI are has been a major hurdle that has slowed progress, with studies reporting the full range of effects: increase, decrease, and no change in anxiety following injury. Here, we addressed this issue directly by investigating long-term anxiety outcomes in mice following a moderate to severe controlled cortical impact (CCI) injury using a battery of standard behavioral tests-the open field (OF), elevated zero maze (EZM), and elevated plus maze (EPM). Mice were tested on weeks 1, 3, 5 and 7 post-injury. Our results show that the effect of injury is time- and task-dependent. Early on-up to 3 weeks post-injury, there is an increase in anxiety-like behaviors in the elevated plus and zero mazes. However, after 5 weeks post-injury, anxiety-like behavior decreases, as measured in the OF and EZM. Immunostaining in the basolateral amygdala (BLA) for GAD, a marker for GABA, at the end of the behavioral testing showed the late decrease in anxiety behavior was correlated with upregulation of inhibition. The approach adopted in this study reveals a complex trajectory of affective outcomes following injury, and highlights the importance of comparing outcomes in different assays and time-points, to ensure that the affective consequences of injury are adequately assessed.

SUBMITTER: Popovitz J

PROVIDER: S-EPMC6351473 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Long-Term Effects of Traumatic Brain Injury on Anxiety-Like Behaviors in Mice: Behavioral and Neural Correlates.

Popovitz Juliana J Mysore Shreesh P SP Adwanikar Hita H

Frontiers in behavioral neuroscience 20190123

Traumatic brain injury (TBI) has been frequently linked to affective disorders such as anxiety and depression. However, much remains to be understood about the underlying molecular and signaling mechanisms that mediate affective dysfunctions following injury. A lack of consensus in animal studies regarding what the affective sequelae of TBI are has been a major hurdle that has slowed progress, with studies reporting the full range of effects: increase, decrease, and no change in anxiety followin ...[more]

PMID: 30728770

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Project description:Introduction: Behavioral disturbances are found in 50-60% of traumatic brain injury (TBI) survivors with an enormous impact on daily functioning and level of recovery. However, whether typical profiles can be distinguished and how these relate to provided care is unclear. The purpose of this study is to specify the characteristics of behavioral disturbances in patients with various severity of TBI and the impact on functional outcome. Furthermore, the pathways of care after hospital discharge for patients and their care givers are analyzed. Methods: We performed a retrospective cohort study comprising 226 patients with mild TBI (mTBI; n = 107) and moderate-to-severe TBI (mod/sevTBI; n = 119) treated at the outpatient clinic and/or rehabilitation center of our university hospital between 2010 and 2015. Inclusion criteria were: behavioral disturbances as determined with the Differential Outcome Scale and age ?16 years. Functional outcome was determined by the Glasgow Outcome Scale Extended and return to work (RTW) at six months to one year post-injury. Behavioral impairments and pathway of care were derived from medical files and scored according to predefined criteria. Results: Overall 24% of patients showed serious behavioral disturbances; three times higher in mod/sevTBI (35%) compared to mTBI (13%). mTBI patients mostly showed irritation (82%) and anger (49%), while mod/sevTBI patients mostly showed irritation (65%) and disinhibition (55%). Most (92%) patients returned home, half of the patients did not RTW. Deficits in judgment and decision-making increased risk of no RTW 10-fold. One in ten patients was (temporarily) admitted to a nursing home or psychiatric institution. 13% Of caregivers received support for dealing with impairments of patients and 13% of the mTBI and 17% of the mod/sevTBI patients experienced relational problems. Conclusions: The spectrum of behavioral disturbances differs between TBI severity categories and serious behavioral disturbances are present in a quarter of patients. Only half of the patients resumed work regardless of severity of injury suggesting that particularly the presence and not the severity of long-term behavioral disturbances interferes with RTW. Most patients returned home despite these behavioral disturbances. These findings underline the importance of early identification and appropriate treatment of behavioral disturbances in TBI patients.

Project description:ObjectiveLong-term changes to EEG spectra after mild traumatic brain injury (mTBI, i.e., concussion) have been reported; however, the role of injury characteristics in long-term EEG changes is unclear. It is also unclear how any chronic EEG changes may underlie either subjective or objective cognitive difficulties, which might help explain the variability in recovery after mTBI.MethodsThis study included resting-state high-density electroencephalography (EEG) and mTBI injury data from 340 service members and veterans collected on average 11 years after injury as well as measures of objective and subjective cognitive functioning. The average absolute power within standard bands was computed across 11 spatial regions of the scalp. To determine how variation in brain function was accounted for by injury characteristics and aspects of cognition, we used regression analyses to investigate how EEG power was predicted by mTBI history characteristics [number, number with post-traumatic amnesia and witnessed loss of consciousness (PTA + LOC), context of injury (combat or non-combat), potentially concussive blast exposures], subjective complaints (TBIQOL General Cognitive and Executive Function Concerns), and cognitive performance (NIH Toolbox Fluid Intelligence and premorbid IQ).ResultsPost-traumatic amnesia (PTA) and loss of consciousness (LOC), poorer cognitive performance, and combat experience were associated with reduced power in beta frequencies. Executive function complaints, lower premorbid IQ, poorer cognitive performance, and higher psychological distress symptoms were associated with greater power of delta frequencies. Multiple regression confirmed the relationship between PTA + LOC, poor cognitive performance, cognitive complaints, and reduced power in beta frequencies and revealed that repetitive mTBI was associated with a higher power in alpha and beta frequencies. By contrast, neither dichotomous classification of the presence and absence of mTBI history nor blast exposures showed a relationship with EEG power variables.ConclusionLong-term alterations in resting EEG spectra measures of brain function do not appear to reflect any lasting effect of a history of mTBI or blast exposures. However, power in higher frequencies reflects both injury characteristics and subjective and objective cognitive difficulties, while power in lower frequencies is related to cognitive functions and psychological distress associated with poor long-term outcomes after mTBI.

Dataset Information

Long-Term Effects of Traumatic Brain Injury on Anxiety-Like Behaviors in Mice: Behavioral and Neural Correlates.

Publications

Long-Term Effects of Traumatic Brain Injury on Anxiety-Like Behaviors in Mice: Behavioral and Neural Correlates.

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