Depletion of Brain Docosahexaenoic Acid Impairs Recovery from Traumatic Brain Injury

Abhishek Desai,Hee-Yong Kim,Karl Kevala,Lucio Annunziato

doi:10.1371/journal.pone.0086472

Abhishek Desai, Hee-Yong Kim + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0086472

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Abstract

Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.

Highlights

Traumatic brain injury (TBI) is a leading cause of death and disability contributing to a third of all injury-related deaths in the USA [1]
LNA serves as the precursor for long chain omega-3 fatty acids such as docosahexaenoic acid (DHA) while LA is converted into long chain omega-6 fatty acids such as arachidonic acid (AA) [3]
The present study demonstrates that i) severe DHA deficiency in the brain impairs functional recovery from TBI in terms of vestibulo-motor and cognitive deficits (ii) DHA deficiency further elevates TBI-induced production of Spectrin breakdown products (SBDPs) (iii) less neurons were found around the injury site of DHA deficient brain after TBI compared to the omega-3 fatty acid adequate group

Summary

Introduction

Traumatic brain injury (TBI) is a leading cause of death and disability contributing to a third of all injury-related deaths in the USA [1]. Mild concussion can lead to temporary state of confusion and transient unconsciousness while severe brain injury may result in loss of function of the limbs, speech impairment, disturbances in normal memory and emotional responses. Supplementation of DHA exerts neuroprotective effects and has been reported to afford protection from diffuse axonal injury [11] and mixed brain injury [12] as well as in Alzheimer’s disease model [13], cerebral ischemia [14,15], and Parkinson’s disease [16,17]. We have investigated the consequence of severe depletion of brain DHA on the behavioral and histological outcome of focal brain injury in a mouse model after manipulating the brain DHA status through multi-generational feeding with an omega-3 fatty acid deficient diet

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