Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury.
BACKGROUND
Although various strategies for prevention of brain disease have been implemented, no substance has been found to be advantageous for prophylaxis against brain injury.


OBJECTIVE
While previous work in our laboratory and others have shown positive effects using the omega-3 fatty acid docosahexaenoic acid (DHA) in post-injury treatment following traumatic and ischemic insults, we wished to test its effects when given prior to injury. We have attempted to measure anatomical, cellular, and behavioral outcomes with a prophylactic administration of DHA.


METHODS
Five groups of 16 adult male Sprague-Dawley rats were subjected to an impact acceleration traumatic brain after having received a prior administration of DHA in doses of 3, 12, and 40 mg/kg for 30 days prior. Serum fatty acid levels were determined from isolated plasma phospholipids at baseline and at the end of 30 days supplementation. Following sacrifice 1 week after injury, brainstem white matter tracts underwent fluorescent immunohistochemical processing for labeling of beta amyloid precursor protein (APP), an anatomical marker of brain injury, as well as measurements of CD68 and caspase-3 levels, and water maze testing was used for behavioral assessment.


RESULTS
Dietary supplementation with DHA resulted in increased serum DHA levels proportionate with the escalating dosage. Immunohistochemical analysis revealed significantly (P < .05) decreased numbers of APP levels in all groups of animals receiving pre-injury supplementation with DHA of 4, 12, and 40 mg/kg at 13955, 4186, and 2827 axons per mm³, respectively, vs 37442 in unsupplemented animals, as measured by stereological methodology. Using a selective measuring technique, only the highest dosage group, 40 mg/kg showed significantly (P < .05) decreased numbers of APP positive axons, at 1.15 axons per high power field vs 6.78 in unsupplemented animals. CD-68, caspase-3, and water maze testing all were significantly (P < .05) improved in the high dose group.


CONCLUSIONS
Dietary supplementation with DHA increases serum levels and, if given prior to traumatic brain injury, reduces the injury response, as measured by axonal injury counts, markers for cellular injury and apoptosis, and memory assessment by water maze testing. This uniform response was seen for the highest dosage group, 40 mg/kg given over 30 days prior to injury, but when measured by stereological counting methodology there was a positive response to anatomical injury across low to high doses of DHA. The potential for DHA to provide prophylactic benefit to the brain against traumatic injury appears promising and requires further investigation.
Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
James D
JD
Mills
Kevin
K
Hadley
Julian E
JE
Bailes
D000818:Animals; D001921:Brain / Q000187:drug effects*; D001930:Brain Injuries / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids