Administration of Riboflavin Improves Behavioral Outcome and Reduces Edema Formation and Glial Fibrillary Acidic Protein Expression after Traumatic Brain Injury

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Abstract
Previous studies have shown that administration of riboflavin, vitamin B2, significantly reduced edema formation following experimental stroke. The present study evaluated the ability of B2 to improve behavioral function, reduce edema formation, and limit glial fibrillary acidic protein (GFAP) expression following frontal cortex contusion injury. Groups of rats were assigned to B2 (7.5 mg/kg) or saline (1.0 ml/kg) treatment conditions and received contusion injuries or sham procedures. Drug treatment was administered 15 min and 24 h following injury. Rats were examined on a variety of tests to measure sensorimotor performance (bilateral tactile removal test), and cognitive ability (acquisition of reference and working memory) in the Morris water maze. Administration of B2 following injury significantly reduced the behavioral impairments observed on the bilateral tactile removal test and improved the acquisition of both reference and working memory tests compared to saline-treated rats. The lesion analysis showed that B2 reduced the size of the lesion. Examination of GFAP expression around the lesion revealed that B2 significantly reduced the number of GFAP+ astrocytes. Edema formation following injury was also significantly reduced by B2 administration. These findings are the first to show that B2 administration significantly improved behavioral outcome and reduced lesion volume, edema formation, and the expression of GFAP following traumatic brain injury. These findings suggest that B2 may have therapeutic potential for the treatment of TBI.