Abstract

Anxiety is a common complaint following acquired traumatic brain injury (TBI). However, the measurement of dysfunctional anxiety behavioral states following experimental TBI in rodents is complex. Some studies report increased anxiety after TBI, whereas others find a decreased anxiety-like state, often described as increased risk-taking behavior or impulsivity. These inconsistencies may reflect a lack of standardization of experimental injury models or of behavioral testing techniques. Here, we review the most commonly employed unconditioned tests of anxiety and discuss them in a context of experimental TBI. Special attention is given to the effects of repeated testing, and consideration of potential sensory and motor confounds in injured rodents. The use of multiple tests and alternative data analysis methods are discussed, as well as the potential for the application of common data elements (CDEs) as a means of providing a format for documentation of experimental details and procedures of each published research report. CDEs may improve the rigor, reproducibility, as well as endpoint for better relating findings with clinical TBI phenotypes and the final goal of translation. While this may not resolve all incongruities in findings across laboratories, it is seen as a way forward for standardized and universal data collection for improvement of data quality and sharing, and advance therapies for neuropsychiatric symptoms that often present for decades following TBI.

Highlights

  • Anxiety disorders are characterized by the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, version 5) as excessive fear and anxiety with related behavioral disturbances (American Psychiatric Association, 2013), and are associated with comorbid conditions such as cardiovascular disease, migraine, hypertension, and gastrointestinal disease

  • It is difficult to make broad conclusions regarding anxiety-like states in rodents following experimental traumatic brain injury (TBI)

  • The employment of unconditioned tests has led to a wide body of literature, yet disparate results for many rodent TBI models, across multiple tests

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Summary

INTRODUCTION

Anxiety disorders are characterized by the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, version 5) as excessive fear and anxiety with related behavioral disturbances (American Psychiatric Association, 2013), and are associated with comorbid conditions such as cardiovascular disease, migraine, hypertension, and gastrointestinal disease. Prior to 1 month following injury, mice with a moderate to severe CCI showed increased anxietylike behaviors in the EZM and EPM, whereas after 5 weeks, decreased anxiety-like behaviors were measured in the EZM and OFT (Popovitz et al, 2019) Both of these studies illustrate the complexity of the changes in behavior and evolution over time in functional changes after TBI, and suggest that a comprehensive approach is necessary for drawing firmer conclusions regarding anxiety symptoms. More data are needed, results with the CHIMERA model have shown relative consistency: increased anxiety is measured in the OFT test up to a couple of weeks following injury, whereas decreased anxiety-like behaviors are found with the EZM or EPM at more chronic time points (e.g., Namjoshi et al, 2014; Nolan et al, 2018; McNamara et al, 2020). Decreased time spent in the light chamber (increased anxiety) and reduced number of transitions

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Findings
SUMMARY AND CONCLUSION
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