Experimental Traumatic Brain Injury Induces a Pervasive Hyperanxious Phenotype in Rats

Abstract

Mood disturbances, including depression and anxiety disorders, are common and disabling long-term sequelae of traumatic brain injury (TBI). These psychiatric conditions have generally been considered psychosocial consequences of the trauma, but neurobiological alterations and causes have also been implicated. Using a rat model of TBI (lateral fluid-percussion injury), this longitudinal study seeks to assess anxiety and depression-like behaviors following experimental TBI. Male Wistar rats (n = 20) received a severe (approximately 3.5 atmosphere) pressure pulse directed to the right sensorimotor cortex, or sham surgery (n = 15). At 1, 3, and 6 months following injury, all rats underwent four assessments of anxiety and depression-like behaviors: exposure to an open field, elevated plus maze test, the forced swim test, and the sucrose preference test. Injured animals displayed increased anxiety-like behaviors throughout the study, as evidenced by reduced time spent (p = 0.014) and reduced entries (p < 0.001) into the center area of the open field, and reduced proportion of time in the open arms of the plus maze (p = 0.015), compared to sham-injured controls. These striking changes were particularly evident 1 and 3 months after injury. No differences were observed in depression-like behaviors in the forced swim test (a measure of behavioral despair) and the sucrose preference test (a measure of anhedonia). This report provides the first evidence of persistent anxiety-like disturbances in an experimental model of TBI. This finding indicates that the common occurrence of these symptoms in human sufferers is likely to have, at least in part, a neurobiological basis. Studies in this model could provide insight into the mechanisms underlying affective disturbance in brain-injured patients.

A CD11d Monoclonal Antibody Treatment Reduces Tissue Injury and Improves Neurological Outcome after Fluid Percussion Brain Injury in Rats

“…Other lateral FPI studies have also found motor, emotional, and cognitive impairments that occurred in the presence of extensive damage to the hippocampus and the frontal, parietal, and temporal cortices (Jones et al, 2008;Wahl et al, 2000). Accordingly, damage to the hippocampus and other areas may have contributed to the behavioral impairments seen in the elevated-plus maze, water maze, and beam task in the 1B7 controls.…”

“…Previous studies have shown that decreased time spent in the open arm of the elevated-plus maze represents an increase in anxiety-like behavior (Jones et al, 2008;Walf and Frye, 2007). The 1B7 control rats spent less time in the open arm of the elevated-plus maze compared to both the sham-injured rats and CD11d mAb-treated rats at 4 weeks after the TBI, suggesting that these rats experienced heightened levels of anxiety, and that the CD11d treatment reduced the anxiogenic effect of lateral FPI.…”

Progressive Metabolic and Structural Cerebral Perturbations After Traumatic Brain Injury: An In Vivo Imaging Study in the Rat

“…Lateral FPI induces both focal and diffuse cerebral injury and is a widely accepted experimental model of moderate-to-severe human closed-head TBI (10,11). The severity of the imag-ing changes was correlated with quantitative measures of anxiety-like behavior, because mood disorders (including hyperanxiety) are common in patients after TBI, and we have demonstrated long-term increases in anxiety-like behavior in rats after FPI (7,12).…”

The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

“…[25][26][27][28] Briefly, anesthesia was induced with 4% isofluorane in oxygen (2 L/min) via inhalation, and maintained throughout surgery with 2% isofluorane and 500 mL/min oxygen flow delivered through a nose cone. Under aseptic conditions, rats underwent craniotomy to create a circular window (5 mm diameter) centered at A/P -3.0 mm, M/L 4.0 mm with reference to bregma to expose the dura mater.…”