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.

Gestational vitamin D deficiency causes permanent changes in the developing rat brain. Not only does it alter brain gene and protein expression, deficiency disrupts the balance between neuronal stem cell proliferation and programmed cell death in the offspring. These data are particularly relevant in light of new work showing a high prevalence of vitamin D deficiency in humans.

While chronic caloric or dietary restriction, characterized by a regular reduction in food intake, improves longevity and reduces the risk of age‐related neurodegenerative disorders and injury following ischemia, its ability to improve outcomes after traumatic brain injury (TBI) has not been explored. Because TBI is a significant problem in aging populations, we hypothesized that caloric restriction would improve learning and memory after TBI. Male Sprague‐Dawley rats were divided into 2 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 mos, a weight‐drop device (300g) was used to produce a 2mm medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n=10) were used as sham‐operated controls. CR resulted in significant learning and memory improvements as measured by Morris Water Maze. After 5 d of training, significantly more CR rats than AL rats were able to find the hidden platform (p<0.05). There was also an approx 80% reduction in the time it took CR rats to find the platform (p<0.05). Additionally, 3 wks post‐injury, there was a significant decrease in the size of the cortical necrotic cavity in CR rats (p<0.05). Work is ongoing to determine the cellular mechanisms at the site of injury and in the hippocampus that are responsible for the role of CR in TBI.

Edema and intracranial pressure associated with traumatic brain injury (TBI) result in poor long‐term clinical outcomes. Thus, we need to improve our understanding of the mechanisms that result in edema and develop new treatments to target water accumulation. Progesterone (PROG) has been shown to reduce edema after TBI. Because 1, 25 dihydroxyvitamin D (D) and PROG both interact with nuclear RXR receptors to regulate gene expression, we hypothesized that acute treatments with the active form of vitamin D could be a useful adjunct to progesterone treatment. TBI was introduced by weight‐drop (300g) creating a 2mm medial frontal cortex contusion following craniotomy in male Fisher rats. Animals were then treated at 1 and 6 hrs post‐injury with vehicle, PROG (16mg/kg), D (2.5 µg/kg), or PROG+D. At 24 h, direct measurements of water accumulation around the site of injury showed that while D alone was ineffective, there was a 4% reduction in water accumulation in PROG treated rats, and a 9% reduction in PROG+D animals. Edema results from vasogenic water accumulation after blood‐brain‐barrier damage and cytotoxic water from cell damage. Water regulating protein aquaporin‐4 was not changed after treatment. Novel in vivo diffusion magnetic resonance imaging at 21 Tesla (21T) allowed us to visualize and distinguish vasogenic and cytotoxic edema. MRI results support that PROG +D protects against vasogenic and cytotoxic edema.