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This study assessed the effect of caffeine on neurobehavioral recovery in the WRAIR penetrating ballistic-like brain injury (PBBI) model. Unilateral frontal PBBI was produced in the right hemisphere of anesthetized rats at moderate (7%-PBBI) or severe (10%-PBBI) injury levels. Animals were randomly assigned to pretreatment groups: acute caffeine (25 mg/kg CAF gavage, 1 h prior to PBBI), or chronic caffeine (0.25 g/L CAF drinking water, 30 days prior to PBBI). Motor function was evaluated on the rotarod at fixed-speed increments of 10, 15, and 20 RPM. Cognitive performance was evaluated on the Morris water maze. Acute caffeine showed no significant treatment effect on motor or cognitive outcome. Acute caffeine exposure prior to 10%-PBBI resulted in a significantly higher thigmotaxic response compared to vehicle-PBBI groups, which may indicate caffeine exacerbates post-injury anxiety/attention decrements. Results of the chronic caffeine study revealed a significant improvement in motor outcome at 7 and 10 days post-injury in the 7%-PBBI group. However, chronic caffeine exposure significantly increased the latency to locate the platform in the Morris water maze task at all injury levels. Results indicate that chronic caffeine consumption prior to a penetrating TBI may provide moderate beneficial effects to motor recovery, but may worsen the neurocognitive outcome.

Differential Effects of Caffeine on Motor and Cognitive Outcomes of Penetrating Ballistic-Like Brain Injury