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.
Highlights
Traumatic brain injury (TBI), characterized as any damage to the brain caused by external acceleration or deceleration forces (Ingebrigtsen and Romner, 2003; Menon et al, 2010), is a complex health problem affecting millions of people worldwide (Hyder et al, 2007)
Mice were tested in the open field (OF), elevated zero maze (EZM) and elevated plus maze (EPM) tests
Anxiety was measured by the change in proportion of time they spent in the anxiogenic zone in each assay, as well as number of entrances to the open arm (EZM and EPM)
Summary
Traumatic brain injury (TBI), characterized as any damage to the brain caused by external acceleration or deceleration forces (Ingebrigtsen and Romner, 2003; Menon et al, 2010), is a complex health problem affecting millions of people worldwide (Hyder et al, 2007). TBI produces considerable and wide-ranging losses in cognitive, motor and affective functions (Draper and Ponsford, 2008; Ponsford et al, 2008). This is true even of injuries considered mild or moderate, which constitute 80% of all cases and can lead to debilitating long-term effects (Buck, 2011; Coronado et al, 2015). Animal models of TBI, and rodent models, have been used to replicate the human symptomatology, examine neural mechanisms and test therapeutic interventions. The cognitive and motor outcomes of TBI have been well established and replicated among pre-clinical studies (Fujimoto et al, 2004; Morales et al, 2005; Shear et al, 2010). Studies in rodents, which typically quantify anxiety as the proportion of time animals spend in a more exposed, anxiogenic portion of a behavioral apparatus, as opposed to an enclosed, less anxiogenic zone, have yielded inconsistent and, at times, contradictory results (Wagner et al, 2007; Wakade et al, 2010; Schultz et al, 2011; Ajao et al, 2012; Cope et al, 2012; Washington et al, 2012; Budinich et al, 2013; Almeida-Suhett et al, 2014; Amorós-Aguilar et al, 2015; SierraMercado et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
