Manifestations of Apprehension and Anxiety in a Sprague Dawley Cranial Defect Model

Background:Syndrome of the trephined is a neurologic condition that commonly arises in patients who undergo craniectomy and have a prolonged cranial defect. Symptoms of this condition include headache, difficulties concentrating, diminished fine motor/dexterity skills, mood changes, and anxiety/apprehension. The authors hypothesize that an animal model demonstrating anxiety/apprehension in rats who undergo craniectomy is feasible utilizing standardized animal behavioral testing.Methods:Sprague Dawley rats were the stratified to 1 of 2 groups for comparison of neurobehavioral outcomes. Group #1 (closed cranial group) had their cranial trephination immediately closed with acrylic to restore normal cranial anatomy and Group #2 (open cranial group) had their cranial trephination enlarged to represent a decompressive hemicraniectomy immediately. Anxiety/apprehension was studied using a standardized rodent open field test. Statistical comparison of differences among the 2 groups was performed.Results:Ten rats were studied with 5 rats in each group. Standard rodent open field testing of anxiety demonstrated no difference among the 2 groups at 1 week. Rats in the "Open cranial group" demonstrated progressively more anxiety over the following 3-month period. Rats in the "Open cranial group" demonstrated increasing anxiety levels as compared with rats in the "Closed cranial group." At week 16, the "Open cranial group" anxiety levels were significantly greater than week 4 (t = 2.24, P = 0.04) demonstrating a significant linear trend over time (R²= 0.99; P = 0.002). The "Closed cranial group" did not show this trend (R²= 07; P = 0.74).Conclusion:Our study demonstrates that anxiety and apprehension are more prevalent in rats with an open, prolonged cranial defect in comparison to those with a closed cranium. This correlates with similar finds in humans with syndrome of the trephined.