Chronic Caloric Restriction Reduces Tissue Damage and Improves Spatial Memory in a Rat Model of Traumatic Brain Injury

Although it has been known for some time that chronic caloric or dietary restriction reduces the risk of neurodegenerative disorders and injury following ischemia, the possible role of chronic restriction in improving outcomes after traumatic brain injury (TBI) has not been previously studied. Therefore, 2-month-old male Sprague-Dawley rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric-restriction group (CR) that was provided with 70% of the food intake of AL rats (n = 10/group). After 4 months, a weight-drop device (300 g) was used to produce a 2-mm bilateral medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n = 10) were used as sham-operated controls. The CR diet resulted in body weights that were reduced by 30% compared with AL controls. Not only did CR decrease the size of the cortical lesion after injury, there were marked improvements in spatial memory as measured by Morris water maze that included an increase in the number of animals successfully finding the platform as well as significantly reduced time to finding the hidden platform. Western analysis, used to examine the expression of proteins that play a role in neuronal survival, revealed significant increases in brain-derived neurotrophic factor (BDNF) in the cortical region around the site of injury and in the hippocampus in CR rats after injury. These findings suggest that molecular mechanisms involved in cell survival may play a role in reducing tissue damage and improving cognition after TBI and that these mechanisms can be regulated by dietary interventions.